Preparation Method for Glufosinate

Abstract

A preparation method for glufosinate or a salt, an enantiomer or a mixture of enantiomers in all ratios thereof, the method being especially suitable for the preparation of glufosinate, and greatly shortening steps in an existing preparation process. Especially in the preparation of L-glufosinate, the product can effectively retain the ee value of the raw materials.

Claims

1-31. (canceled)

32. A method for preparing glufosinate of formula (I) or a salt, an enantiomer thereof or a mixture of the enantiomers in all ratios, characterized in that the method comprises the following steps: ##STR00073## a) reacting a compound of formula (II) or a salt, an enantiomer thereof or a mixture of the enantiomers in all ratios, ##STR00074## with one or more compounds of formula (III) or a mixture; the mixture being a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V); or a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (V) and one or more compounds of formula (III); or a mixture comprising one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V); ##STR00075## ##STR00076## ##STR00077## b) reacting the intermediate, no matter whether it is isolated or not, in the presence of water and an acid or a base to obtain the glufosinate (I) or a salt, an enantiomer thereof or a mixture of the enantiomers in all ratios; wherein when PG is an amino protecting group, a step of removing the amino protecting group can be further comprised; wherein: LG is Hal.sup.1, -OTs or ##STR00078## Hal.sup.1 and Hal.sup.2 are each independently halogen, e.g., fluorine, chlorine, bromine or iodine; PG is hydrogen or an amino protecting group, and the amino protecting group preferably is -C(=O)R, -C(=O)OR or -S(=O).sub.2R; A is -NHR.sub.1, -NR.sub.1R.sub.1, or -OR.sub.1; R, R.sub.1, R.sub.1′, R.sub.2, R.sub.3 and R.sub.4 are each independently selected from the group consisting of C.sub.1-C.sub.6 alkyl, C.sub.3-10 cycloalkyl, C.sub.6-10 aryl, C.sub.6-12 aralkyl, 5- to 14-membered heteroaryl and 3- to 10-membered heterocyclyl, and when the mixture comprises the mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), or when the mixture comprises the mixture of one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V), R.sub.2 is either R.sub.3 or R.sub.4; and the chiral carbon atom is labeled with *; and provided that at least one of the following conditions is met: 1) the compound of formula (II) is not ##STR00079## 2) the compound of formula (III) is not ##STR00080## 3) the compound of formula (IV) is not ##STR00081## 4) the compound of formula (V) is not ##STR00082## .

33. The method according to claim 32, wherein the glufosinate of formula (I) or a salt thereof prepared by the method is enantiomerically pure, ##STR00083## characterized in that the compound of the formula (II) in the step a) is enantiomerically pure.

34. The method according to claim 32, characterized in that the enantiomeric ratio is (L): (D)-enantiomer or (D):(L)-enantiomer of 50.5:49.5 to 99.5:0.5.

35. The method according to claim 32, characterized in that R is C.sub.1-C.sub.6 alkyl or C.sub.6-10 aryl, preferably is methyl, ethyl, tert-butyl, phenyl or p-methylphenyl; preferably, the PG is hydrogen, -C(=O)CH.sub.3, -C(=O)Ph, -C(=O)OC.sub.2H.sub.5, -C(=O)OC(CH.sub.3).sub.3 or ##STR00084## .

36. The method according to claim 32, characterized in that the Hal.sup.1 is chlorine, bromine or iodine; preferably, LG is chlorine, bromine, iodine, -OTs or ##STR00085## more preferably, LG is chlorine, bromine or iodine; or the Hal.sup.2 is chlorine.

37. The method according to claim 32, characterized in that the R.sub.1, R.sub.1′, R.sub.2, R.sub.3 and R.sub.4 are each independently C.sub.1-C.sub.6 alkyl or C.sub.6-12 aralkyl, preferably are C.sub.1-C.sub.4 alkyl or benzyl.

38. The method according to claim 32, characterized in that the R.sub.1 and R.sub.1′ are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or benzyl; preferably, A is -NHCH.sub.2CH.sub.2CH.sub.2CH.sub.3, -N(CH.sub.3).sub.2, -OCH.sub.3, -OCH.sub.2CH.sub.3, -OCH.sub.2CH.sub.2CH.sub.3, -OCH(CH.sub.3).sub.2, OCH.sub.2CH.sub.2CH.sub.2CH.sub.3, -OCH.sub.2CH(CH.sub.3).sub.2 or -OBn.

39. The method according to claim 32, characterized in that the R.sub.2 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl, preferably is n-propyl, isopropyl or n-butyl; or R.sub.3 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl, preferably is n-propyl, isopropyl or n-butyl; or R.sub.4 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl, preferably is n-propyl, isopropyl or n-butyl.

40. The method according to claim 32, characterized in that the mixture is a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III), and the molar ratio of the compounds of formula (IV) to the compounds of formula (III) is (0.9-1.1): 1 or (0.05-1.1): 1; or the mixture is a mixture of one or more compounds of formula (V) and one or more compounds of formula (III), and the molar ratio of the compounds of formula (V) to the compounds of formula (III) is (0.9-1.1): 1 or (0.05-1.1): 1; or the mixture is a mixture comprising one or more compounds of formula (IV) and one or more compounds of formula (V), and the molar ratio of the compounds of formula (IV) to the compounds of formula (V) is (0.9-1.1):1.

41. The method according to claim 32, characterized in that in the step a), the reaction temperature is 20 to 200° C., preferably 90 to 140° C.

42. The method according to claim 32, characterized in that the step a) is carried out in the presence of a base.

43. The method according to claim 42, characterized in that the base in the step a) is an organic base selected from the group consisting of an organic amine, pyridine or a pyridine derivative having 1-3 substituents attached to one or more carbon atoms in the heterocycle, piperidine or a piperidine derivative having 1-3 substituents attached to one or more carbon atoms in the heterocycle or ammonia.

44. The method according to claim 43, characterized in that the organic base is selected from the group consisting of triethylamine, piperidine or pyridine.

45. The method according to claim 32, characterized in that in the step a), the molar ratio of the base to the total amounts of the compound of formula (III) and the compound of formula (V) is (1-10):1.

46. The method according to claim 32, characterized in that in the step a), the reaction is carried out under a solvent-free condition or in an inert solvent.

47. The method according to claim 32, characterized in that in the step a), the inert solvent is selected from any one or more of benzene solvents, amide solvents, hydrocarbon solvents, halogenated hydrocarbon solvents, sulfone or sulfoxide solvents, ether solvents or ester solvents; preferably, the inert solvent is selected from any one or more of benzene solvents, amide solvents, halogenated hydrocarbon solvents, ether solvents or ester solvents.

48. The method according to claim 46, characterized in that in the step a), the inert solvent is selected from any one or more of chlorobenzene, trimethylbenzene, 1,4-dioxane, 1,2-dichloroethane, dimethyl sulfoxide, N-methylpyrrolidone, N,N-dimethylformamide, petroleum ether, n-heptane, tetrahydrofuran, methyltetrahydrofuran, benzene, toluene, ethyl acetate, and butyl acetate.

49. The method according to claim 32, characterized in that in the step a), the molar ratio of the compound of formula (III) or the mixture to the compound of formula (II) is 1:(0.8-10), preferably 1:(1-3); or the molar ratio of the compound of formula (II) to the compound of formula (III) or the mixture is 1:(0.8-10), preferably 1:(1-3).

50. The method according to claim 32, characterized in that in the step b), an inorganic acid or an organic acid is added.

51. The method according to claim 50, characterized in that the inorganic acid is hydrochloric acid or sulfuric acid.

52. The method according to claim 32, characterized in that in the step b), the base is an inorganic base selected from the group consisting of alkali metal hydroxide, alkali-earth metal hydroxide, alkali metal carbonate, alkali-earth metal carbonate, alkali metal bicarbonate or alkali-earth metal bicarbonate or an organic base.

53. The method according to claim 52, characterized in that the base is NaOH, KOH or Ba(OH).sub.2.

54. The method according to claim 32, characterized in that in the step b), the reaction temperature is 20 to 150° C.

55. The method according to claim 32, characterized in that the compound of formula (II) is selected from the group consisting of: TABLE-US-00004 No. The compound of formula (II) 1. 2. 3. 4. 5. 6. 7. 8. 9. TABLE-US-00005 10. 11. 12. 13. 14. and/or, the compound of formula (IV) is ##STR00100## ##STR00101## ##STR00102## compound of formula (V) is ##STR00103## .

56. A compound of formula (II) or a salt thereof, ##STR00104## wherein the compound of formula (II) is selected from the group consisting of: ##STR00105## ##STR00106## .

57. A method for preparing glufosinate or a salt thereof, or L-glufosinate or a salt thereof, wherein the method comprises a step of using the compound according to claim 56.

Description

DETAILED DESCRIPTION OF THE INVENTION

Example 1a: General Preparation Method for Compounds 1-5

[0082] ##STR00028##

[0083] L-homoserine lactone hydrochloride (1a-1) (ee value of 99%, 0.1 mol) was added to a round bottom flask, and alcohol (the molar ratio of homoserine lactone hydrochloride to alcohol was about 1:(10~15)) was added. The temperature of the system was lowered to 10° C., and thionyl chloride (0.3 mol) was slowly dropwise added. The system temperature was maintained at 10° C., and stirred for 30 min. The temperature was gradually raised to 35° C., and the reaction was stirred for 20 hours, during which bubbles were continuously generated. The reaction was monitored by LC-MS or LC, until the reaction was complete (for complete reaction of certain substrates, raising reaction temperature was necessary). The temperature of the system was lowered to room temperature, the remaining thionyl chloride and solvent were distilled off under reduced pressure, the solid residue was slurried with 100 mL of a mixed solvent of n-hexane and ethyl acetate (the volume ratio of n-hexane to ethyl acetate was 2:1), and the filter cake was obtained through filtration. The wet product 1a-2 was neutralized with ammonia water, the system was adjusted to pH 7-8, and extracted with ethyl acetate. The organic phase was collected, dried and concentrated to obtain the target product compound 1a-3.

Example 1b: Preparation of Compound 16

[0084] ##STR00029##

Step 1

[0085] The synthesis was conducted using compound 16-1 as the starting material (the synthesis described in Weitz, Iris S. et al., Journal of Organic Chemistry (1997), 62(8), 2527-2534, can be referred to). At room temperature, compound 16-1 (40 mmol), DCM (20 ml), carbon tetrachloride (20 ml) and triphenylphosphine (120 mmol) were added to a round bottom flask, and then stirred at room temperature for 2 hours. TLC indicated that the raw materials underwent a complete reaction, and compound 16-2 was obtained by column chromatography at a yield of 50%.

[0086] MS (ESI): m/z [M+H].sup.+ calculated for C.sub.11H.sub.22ClN.sub.2O.sub.3: 265.13; found: 265.1.

[0087] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 4.84 (td, J = 8.8, 4.0 Hz, 1H), 3.80 - 3.44 (m, 2H), 3.12 (s, 3H), 2.97 (s, 3H), 2.16 - 2.03 (m, 1H), 1.96 (ddt, J = 14.5, 8.9, 5.6 Hz, 1H), 1.43 (s, 9H).

Step 2

[0088] Compound 16-2 (20 mmol) was added to a round bottom flask, followed by addition of 1,4-dioxane (60 ml) and 36% HCl (16 ml), and the reaction was stirred at room temperature overnight. The reaction solution was concentrated, and then ammonia water was added for neutralization, with the pH being adjusted to 7-8. The mixture was extracted with ethyl acetate, dried and concentrated to obtain compound 16.

[0089] Homoserine analogues in the following table were prepared by the methods of Example 1a, Example 1b or similar methods known in the art.

TABLE-US-00001 No. Homoserine analogue Brief description of the preparation method Characterization data 1. [00030] The alcohol in Example 1a was replaced with methanol. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.5H.sub.11ClNO.sub.2: 152.05; found: 152.1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 3.74 - 3.55 (m, 6H), 2.47 (s, 2H), 2.19 - 2.09 (m, 1H), 1.96 -1.82 (m, 1H). 2. [00031] The alcohol in Example 1a was replaced with n-propanol. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.7H.sub.15ClNO.sub.2: 180.08; found: 180.1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 3.98 (tt, J = 7.1, 3.6 Hz, 2H), 3.69 - 3.49 (m, 3H), 2.10 (ddt, J = 14.1, 8.3, 5.6 Hz, 1H), 1.82 (ddt, J = 14.5, 9.0, 5.6 Hz, 1H), 1.73 (s, 2H), 1.61 - 1.52 (m, 2H), 0.85 (t, J = 7.4 Hz, 3H). 3. [00032] The alcohol in Example 1a was replaced with isopropanol. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.7H.sub.15ClNO.sub.2: 180.08; found: 180.1. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 4.91 (td, J = 6.3, 1.6 Hz, 1H), 3.81 - 3.62 (m, 2H), 3.39 (dt, J = 9.3, 3.6 Hz, 1H), 2.05 - 1.93 (m, 1H), 1.93 - 1.70 (m, 3H), 1.20 (t, J = 5.7 Hz, 6H). .sup.13C NMR (100 MHz, DMSO-d.sub.6) δ 174.7, 67.5, 51.5, 42.1, 37.04, 21.5. 4. [00033] The alcohol in Example 1a was replaced with n-butanol. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.8H.sub.17ClNO.sub.2: 194.10; found: 194.1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 4.05 (tt, J = 6.7, 3.4 Hz, 2H), 3.72 - 3.49 (m, 3H), 2.20 - 2.07 (m, 1H), 1.95 (s, 2H), 1.85 (ddt, J = 14.4, 8.9, 5.6 Hz, 1H), 1.61 - 1.51 (m, 2H), 1.31 (h, J = 7.6 Hz, 2H), 0.86 (q, J = 6.9 Hz, 3H). 5. [00034] The alcohol in Example 1a was replaced with isobutanol. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.8H.sub.J7ClNO.sub.2: 194.10; found: 194.1. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 3.92 - 3.65 (m, 4H), 3.48 (dd, J = 9.1, 4.5 Hz, 1H), 2.16 -1.73 (m, 5H), 0.90 (d, J = 6.8 Hz, 6H). .sup.13C NMR (100 MHz, DMSO-d.sub.6) δ 175.1, 70.0, 51.5, 42.1, 37.1, 27.3, 18.8. 6. [00035] It was prepared according to a method similar to that disclosed in WO 2006117552 A1. ---- 7. [00036] It was prepared according to a method disclosed in WO 98/58256. ---- 8. [00037] It was prepared according to a method similar to that disclosed in Journal of Organic Chemistry (2007), 72(21), 8046-8053. MS (ESI): m/z M.sup.+ calculated for C.sub.10H.sub.20NO.sub.3S.sup.+: 234.12; found: 234.1 .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.36 (dd, J = 8.1, 2.8 Hz, 1H), 4.35 (dddd, J = 10.5, 7.7, 4.7, 2.4 Hz, 1H), 4.10 (qd, J = 7.1, 2.1 Hz, 2H), 3.36 (ddt, J = 11.9, 5.8, 2.9 Hz, 2H), 2.95 (dd, J = 4.5, 2.6 Hz, 6H), 2.28 - 2.11 (m, 1H), 2.11 - 1.95 (m, 1H), 1.87 (d, J = 1.3 Hz, 3H), 1.18 (td, J = 7.1, 2.1 Hz, 3H). .sup.13C NMR (100 MHz, DMSO-d.sub.6) δ 170.7, 169.7, 61.0, 50.6, 25.2, 24.4, 22.5, 14.0. 9. [00038] It was prepared according to a method similar to that disclosed in CN 110386882 A. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.13H.sub.17ClNO.sub.3: 270.09; found: 270.1. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.80 (d, J = 7.6 Hz, 1H), 8.01 - 7.76 (m, 2H), 7.60 - 7.53 (m, 1H), 7.49 (t, J = 7.3 Hz, 2H), 4.61 (ddd, J = 9.6, 7.6, 5.0 Hz, 1H), 4.13 (qd, J = 7.1, 1.8 Hz, 2H), 3.89 - 3.62 (m, 2H), 2.36 - 2.13 (m, 2H), 1.19 (t, J = 7.1 Hz, 3H). .sup.13C NMR (100 MHz, DMSO-d.sub.6) δ 171.5, 166.8, 133.6, 131.6, 128.3, 127.5, 60.8, 50.3, 41.9, 33.3, 14.1. 10. [00039] It was prepared according to a method similar to that disclosed in CN 110386882 A. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.13H.sub.19ClNO.sub.4S: 320.07; found: 320.1. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.32 (d, J = 9.0 Hz, 1H), 7.64 (dd, J = 8.2, 1.6 Hz, 2H), 7.44 - 7.30 (m, 2H), 3.95 (tdd, J = 8.9, 6.3, 2.2 Hz, 1H), 3.85 (q, J = 7.1 Hz, 2H), 3.59 (dt, J = 11.3, 5.7 Hz, 1H), 3.51 (ddd, J = 11.0, 8.1, 5.7 Hz, 1H), 2.43 - 2.25 (m, 3H), 1.97 (ttd, J = 14.3, 10.4, 9.2, 7.4 Hz, 2H), 1.02 (t, J = 7.1 Hz, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) δ 170.6, 142.7, 138.1, 129.4, 126.5, 60.9, 53.0, 41.0, 34.8, 20.9, 13.7. 11. [00040] It was prepared according to a method disclosed in WO 2020/145514 A1. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.8H.sub.15ClNO.sub.3: 208.08; found: 208.1. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 8.31 (d, J = 7.7 Hz, 1H), 4.37 (ddd, J = 9.4, 7.6, 4.9 Hz, 1H), 4.09 (qd, J = 7.1, 1.8 Hz, 2H), 3.83 - 3.44 (m, 2H), 2.08 (dddd, J = 20.1, 14.4, 8.2, 4.2 Hz, 2H), 1.86 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H). .sup.13C NMR (100 MHz, DMSO-d.sub.6) δ 171.6, 169.6, 60.7, 49.6, 41.5, 33.7, 22.3, 14.0. 12. [00041] It was prepared according to a method disclosed in CN 110386882 A MS (ESI): m/z [M+H].sup.+ calculated for C.sub.9H.sub.17ClNO.sub.4: 238.09; found: 238.1. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 7.60 (d, J = 8.0 Hz, 1H), 4.14 (dddt, J = 27.3, 9.5, 7.1, 3.7 Hz, 3H), 4.00 (q, J = 7.1 Hz, 2H), 3.82 - 3.46 (m, 2H), 2.08 (ddt, J = 13.1, 8.9, 4.7 Hz, 2H), 1.18 (q, J = 6.9 Hz, 6H). 13. [00042] It was prepared according to a method reported in J. Med. Chem. 1994, 37, 2950-2957. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.11H.sub.21ClNO.sub.4: 266.12; found: 266.2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 7.33 (d, J = 8.0 Hz, 1H), 4.53 - 3.93 (m, 3H), 3.65 (tdd, J = 14.7, 11.0, 6.2 Hz, 2H), 2.36 - 1.90 (m, 2H), 1.38 (s, 9H), 1.18 (td, J = 7.1, 3.1 Hz, 3H). .sup.13C NMR (100 MHz, DMSO-d.sub.6) δ 172.0, 155.6, 78.4, 60.6, 51.1, 41.7, 33.4, 28.1, 14.0. 14. [00043] [00044]Compound 16-1 in Example 1b was replaced with MS (ESI): m/z [M+H].sup.+ calculated for C.sub.7H.sub.16ClN.sub.2O: 179.10; found: 179.1. .sup.1H NMR (400 MHz, D.sub.2O) δ 4.06 (t, J = 6.9 Hz, 1H), 3.93 (p, J = 6.6 Hz, 1H), 3.78 - 3.54 (m, 2H), 2.31 (qd, J = 6.7, 2.0 Hz, 2H), 1.13 (dd, J = 6.6, 2.4 Hz, 6H). .sup.13C NMR (100 MHz, D.sub.2O) δ 167.5, 51.3, 42.3, 39.7, 33.4, 21.2, 21.1. 15. [00045] [00046]Compound 16-1 in Example 1b was replaced with MS (ESI): m/z [M+H].sup.+ calculated for C.sub.8H.sub.18ClN.sub.2O: 193.11; found: 193.1. .sup.1H NMR (400 MHz, D.sub.2O) δ 4.18 (t, J = 6.9 Hz, 1H), 3.79 - 3.65 (m, 2H), 3.33 (dt, J = 13.8, 7.0 Hz, 1H), 3.22 (dt, J = 13.6, 6.9 Hz, 1H), 2.42 - 2.31 (m, 2H), 1.59 - 1.49 (m, 2H), 1.41 - 1.26 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H). .sup.13C NMR (100 MHz, D.sub.2O) δ 168.5, 51.4, 39.8, 39.5, 33.5, 30.2, 19.4, 13.0. 16. [00047] See Example 1b MS (ESI): m/z [M+H].sup.+ calculated for C.sub.6H.sub.14ClN.sub.2O: 165.08; found: 165.1. .sup.1H NMR (400 MHz, D.sub.2O) δ 4.65 (dd, J = 7.7, 4.8 Hz, 1H), 3.79 - 3.64 (m, 2H), 3.09 (s, 3H), 2.93 (s, 3H), 2.30 (dddd, J = 13.7, 11.2, 7.7, 3.9 Hz, 2H). .sup.13C NMR (100 MHz, D.sub.2O) δ 168.5, 48.6, 39.8, 37.1, 35.9, 32.6. 17. [00048] It was prepared according to a method similar to that disclosed in Journal of Organic Chemistry (1986), 51(26), 5047-50. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.15H.sub.22NO.sub.6S: 344.40; found: 344.4. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 7.93 - 7.49 (m, 2H), 7.36 - 7.17 (m, 2H), 5.85 (d, J = 9.1 Hz, 1H), 4.24 - 4.06 (m, 2H), 4.06 - 3.92 (m, 3H), 2.41 (s, 3H), 2.14 - 2.03 (m, 1H), 2.00 (s, 4H), 1.11 (t, J= 7.1 Hz, 3H). .sup.13C NMR (100 MHz, CDCl.sub.3) δ 171.1, 170.6, 143.5, 136.6, 129.5, 127.1, 61.7, 59.8, 52.8, 31.8, 21.3, 20.6, 13.7.

Example 2

[0090] ##STR00049##

[0091] At -10° C., n-propanol (0.9 mol), triethylamine (0.9 mol) and n-hexane (450 ml) were added to a round bottom flask, and dichloro(methyl)phosphane (0.45 mol) was added dropwise through a constant-pressure dropping funnel for about 1 hour. The reaction was warmed to 0° C., and allowed to proceed for 2 hours for complete reaction. The mixture was filtered, the solid was washed with n-hexane (150 ml × 2), and the mother liquor was evaporated under reduced pressure to remove the solvent. Dipropyl methylphosphonite (colorless liquid, yield: 86%, content: 94%) was obtained through fractionation (the fractionation temperature is not higher than 60° C.).

[0092] MS (ESI): m/z [M+H].sup.+ calculated for C.sub.7H.sub.18O.sub.2P: 165.11; found: 165.1.

[0093] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 3.65 (ddddt, J = 10.0, 6.2, 5.0, 3.5, 1.7 Hz, 4H), 1.51 (q, J = 7.1 Hz, 4H), 1.12 (dd, J = 8.3, 1.2 Hz, 3H), 0.82 (td, J = 7.4, 1.1 Hz, 6H).

[0094] .sup.13C NMR (100 MHz, CDCl.sub.3) δ 68.2, 24.6, 19.9, 10.2.

[0095] .sup.31P NMR (160 MHz, CDCl.sub.3) δ 33.5.

[0096] The following compounds were prepared according to a method similar to that described above.

TABLE-US-00002 No. Alkyl phosphonite Difference as compared with the method in Example 2 Characterization data 1 [00050] n-propanol was replaced with isopropanol. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.7H.sub.18O.sub.2P: 165.11; found: 165.1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 4.11 (dp, J = 9.6, 6.2 Hz, 2H), 1.18 - 1.06 (m, 15H). .sup.13C NMR (100 MHz, CDCl.sub.3) δ 70.3, 24.7, 21.5. .sup.31P NMR (160 MHz, CDCl.sub.3) δ 30.1. 2 [00051] n-propanol was replaced with n-butanol. MS (ESI): m/z [M+H].sup.+ calculated for C.sub.9H.sub.22O.sub.2P: 193.14; found: 193.1. .sup.1H NMR (400 MHz, CDCl.sub.3) δ 3.70 (pd, J = 7.5, 7.1, 3.3 Hz, 4H), 1.53 -1.43 (m, 4H), 1.35 - 1.22 (m, 4H), 1.15 - 1.07 (m, 3H), 0.83 (qd, J = 7.3, 6.8, 3.3 Hz, 6H). .sup.13C NMR (100 MHz, CDCl.sub.3) δ 66.3, 33.5, 20.0, 19.0, 13.7. .sup.31P NMR (160 MHz, CDCl.sub.3) δ 28.7.

Example 3

[0097] ##STR00052##

[0098] Under a nitrogen atmosphere, at -10° C., a solution of a compound of Formula (IV) (0.6 eq, 90% purity) in chlorobenzene was added to a round bottom flask, and a solution of dichloro(methyl)phosphane (0.6 eq, 98% purity) in chlorobenzene was added dropwise through a constant-pressure dropping funnel at a rate of 1 d/s. After the dropwise addition was complete, the reaction was stirred for 10 min (at this time, the corresponding compound of Formula (III)

##STR00053##

could be generated, wherein Hal.sup.2 is chlorine, and R.sub.2 is either R.sub.3 or R.sub.4). Subsequently, a solution of a compound of Formula (IIa) (1.0 eq) and triethylamine (1.2 eq, 98% purity) in chlorobenzene was added thereto at a rate of 4 d/s, and the stirring was continued for 30 min after the dropwise addition. The reaction was warmed to room temperature and stirred for 1h, and then the temperature was raised to 90° C., and the reaction was continued for 12h. The reaction was naturally cooled to room temperature, filtered with suction, and the filter cake was washed with chlorobenzene (150 mL x 3). The filtrate was rotary evaporated to remove chlorobenzene, resulting in an intermediate. The intermediate was added with 100 mL concentrated hydrochloric acid (36%), heated to 90° C., and the reaction was allowed to proceed for 10h. MS detection indicated that the intermediate disappeared, the mixture was naturally cooled to room temperature, rotary evaporated to remove the solvent, and added with 95% ethanol (300 mL). The solution was heated to reflux until the crude product was completely dissolved, naturally cooled for crystallization, filtered and dried to obtain L-glufosinate hydrochloride.

[0099] According to the above method, L-glufosinate hydrochloride was prepared from the substrates in the table below. The reaction yield and ee value of the product are shown in the table below.

TABLE-US-00003 No. Compound of Formula (IIa) Compound of Formula (IV) Yield ee value 1. [00054] [00055] 76% 98% 2. [00056] 78.2% 98% 3. [00057] 65.1% 95% 4. [00058] 79.7% 98% 5. [00059] 48.4% 99% 6. [00060] 24.8% 65% 7. [00061] 38% 86% 8. [00062] 70.80% 96% 9. [00063] 34.1% 93% 10. [00064] 35% 97% 11. [00065] 19.4% 53% 12. [00066] 22% 91% 13. [00067] 43% 73% 14. [00068] [00069] 82% 97% 15. [00070] 74.5% 95%

Example 4

[0100] ##STR00071##

[0101] Under a nitrogen atmosphere, at -10° C., a solution of diethyl methylphosphonite (861.7 g, 0.55 eq, 90% purity) in chlorobenzene (6.0 kg) was added to a 20 L Jacketed Glass Reactor, and a solution of dichloro(methyl)phosphane (679.5 g, 0.55 eq, 98% purity) in chlorobenzene (2.0 kg) was added dropwise through a constant-pressure dropping funnel at a rate of 5 d/s. After the dropwise addition was complete, the reaction was stirred for 10 min (at this time, chloro(ethoxy)(methyl)phosphane

##STR00072##

could be generated). Subsequently, a solution of the compound of Formula (IIa)-butly ester (2.0 kg, 1.0 eq) and triethylamine (1.2 kg, 1.1 eq, 98% purity) in chlorobenzene (8.0 kg) was added thereto at a rate of 10 d/s, and the stirring was continued for 30 min after the dropwise addition. The reaction was warmed to room temperature and stirred for 30 min, and then the temperature was raised to 90° C., and the reaction was continued for 2 h. The reaction was naturally cooled to room temperature, filtered with suction, and the filter cake was washed with chlorobenzene (2.5 L x 2). The filtrate was rotary evaporated to remove chlorobenzene, resulting in an intermediate. The intermediate was added with 4.2 kg 36% wt. hydrochloric acid, heated to 95° C., and the reaction was allowed to proceed for 10 h, and at thesame time, butanol generated was distilled off. MS detection indicated that the intermediate disappeared, the mixture was naturally cooled to room temperature, rotary evaporated to remove the solvent, and added with 95% ethanol (6 L). The solution was heated to reflux until the crude product was completely dissolved, naturally cooled for crystallization, filtered and dried to obtain L-glufosinate hydrochloride (white, yield 88%, ee value 98%).

[0102] In addition to those described herein, according to the foregoing description, various modifications to the present invention would be apparent to those skilled in the art. Such modifications are intended to fall within the scope of the appended claims. Each reference cited herein (including all patents, patent applications, journal articles, books and any other disclosures) are incorporated herein by reference in its entirety.