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. A method for preparing a glufosinate compound of formula (I), a salt thereof, an enantiomer thereof, or a mixture of enantiomers thereof, which enantiomers may be present in any ratio, wherein the method comprises the following steps: ##STR00067## a) reacting a compound of formula (II) or a salt thereof, an enantiomer thereof or a mixture of enantiomers thereof, which enantiomers may be present in any ratio, ##STR00068## with one or more compounds of formula (III) or a mixture; wherein said mixture comprises one or more compounds of formula (IV) and one or more compounds of formula (V); or one or more compounds of formula (IV) and one or more compounds of formula (III); or one or more compounds of formula (V) and one or more compounds of formula (III); or one or more compounds of formula (III), one or more compounds of formula (IV), and one or more compounds of formula (V), wherein the reaction of a) results in a reaction intermediate; ##STR00069## b) reacting the reaction intermediate which results from step a), wherein said reaction intermediate may or may not be in isolated form, with an acid or a base to obtain a glufosinate compound of formula (I) or a salt thereof, an enantiomer thereof, or a mixture of enantiomers thereof, which enantiomers may be present in any ratio; wherein when PG is an amino protecting group, the method further optionally includes the removal of the amino protecting group; further wherein: LG is Hal.sup.1, OTs or Hal.sup.1 ##STR00070## Hal.sup.1 and Hal.sup.2 are each independently halogen selected from fluorine, chlorine, bromine or iodine; PG is hydrogen or an amino protecting group selected from C(O)R, C(O)OR and 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, with the further proviso that when the mixture comprises a mixture of one or more compounds of formula (IV) and one or more compounds of formula (III); or a mixture of one or more compounds of formula (III), one or more compounds of formula (IV) and one or more compounds of formula (V); then R.sub.2 is either R.sub.3 or R.sub.4; and the chiral carbon atom is labeled with *; and with the further proviso that at least one of the following conditions is met: 1) the compound of formula (II) is not ##STR00071## 2) the compound of formula (III) is not ##STR00072## 3) the compound of formula (IV) is not ##STR00073## 4) the compound of formula (V) is not ##STR00074##

2. The method according to claim 1, wherein the glufosinate compound of formula (I) or salt thereof which results from the method is enantiomerically pure, ##STR00075## and wherein the compound of formula (II) in step a) is enantiomerically pure.

3. The method according to claim 1, wherein the enantiomeric ratio of (L):(D)-enantiomer or (D):(L)-enantiomer ranges from 50.5:49.5 to 99.5:0.5.

4. The method according to claim 1, wherein R is C.sub.1-6 alkyl or C.sub.6-10 aryl.

5. The method according to claim 1, wherein LG is chlorine, bromine, iodine, OTs or ##STR00076##

6. The method according to claim 1, wherein 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.

7. The method according to claim 1, wherein R.sub.1 and R.sub.1 are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or benzyl; or 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.

8. The method according to claim 1, wherein R.sub.2 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; or R.sub.3 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl; or R.sub.4 is methyl, ethyl, n-propyl, isopropyl, n-butyl or isobutyl.

9. The method according to claim 1, wherein the mixture comprises 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) ranges from 0.9:1 to 1.1:1 or 0.05:1 to 1.1:1; or the mixture comprises 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) ranges from 0.9:1 to 1.1:1 or 0.05:1 to 1.1:1; or the mixture comprises 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) ranges from 0.9:1 to 1.1:1.

10. The method according to claim 1, where in step a), the reaction temperature ranges from 20 C. to 200 C.

11. The method according to claim 1, where the reaction of step a) is conducted in the presence of a base.

12. The method according to claim 11, wherein the base in the reaction of 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.

13. The method according to claim 12, wherein the organic base is selected from the group consisting of triethylamine, piperidine and pyridine.

14. The method according to claim 1, wherein in step a), the molar ratio of the base to the total amount of the compound of formula (III) and the compound of formula (V) ranges from 1:1 to 10:1.

15. The method according to claim 1, wherein in step a), the reaction is conducted under solvent-free conditions or in the presence of an inert solvent.

16. The method according to claim 15, wherein in 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.

17. The method according to claim 15, wherein in step a), the inert solvent comprises 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.

18. The method according to claim 1, wherein in step a), the molar ratio of the compound of formula (III) or the mixture to the compound of formula (II) ranges from 1:0.8 to 1:10; or the molar ratio of the compound of formula (II) to the compound of formula (III) or the mixture ranges from 1:0.8 to 1:10.

19. The method according to claim 1, wherein in step b), an inorganic acid or organic acid is added.

20. The method according to claim 19, wherein the inorganic acid is hydrochloric acid or sulfuric acid.

21. The method according to claim 1, wherein in step b), the base is an inorganic or organic base, wherein the inorganic base is selected from the group consisting of alkali metal hydroxide, alkali-earth metal hydroxide, alkali metal carbonate, alkali-earth metal carbonate, alkali metal bicarbonate and alkali-earth metal bicarbonate.

22. The method according to claim 21, wherein the base is NaOH, KOH or Ba(OH).sub.2.

23. The method according to claim 1, wherein in step b), the reaction temperature ranges from 20 to 150 C.

24. The method according to claim 1, wherein 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. 10. 11. 12. 13. 14. and/or, the compound of formula IV is ##STR00091## and/or the compound of formula (V) is ##STR00092##

25. A compound of formula (II) or a salt thereof, ##STR00093## wherein the compound of formula (II) is selected from the group consisting of: ##STR00094##

26. The method according to claim 4, wherein R is methyl, ethyl, tert-butyl, phenyl or p-methylphenyl.

27. The method according to claim 1, wherein 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 ##STR00095##

28. The method according to claim 6, wherein R.sub.1, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each independently C.sub.1-C.sub.4 alkyl or benzyl.

29. The method according to claim 1, wherein in step a), the reaction temperature ranges from 90 C. to 140 C.

30. The method according to claim 1, wherein in step a), the molar ratio of the compound of formula (III) or the mixture to the compound of formula (II) ranges from 1:1 to 1:3; or the molar ratio of the compound of formula (II) to the compound of formula (III) or the mixture ranges from 1:1 to 1:3.

Description

DETAILED DESCRIPTION OF THE INVENTION

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

(1) ##STR00022##

(2) 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:(1015)) 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

(3) ##STR00023##

(4) 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%.

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

(6) .sup.1H NMR (400 MHz, CDCl.sub.3) 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

(7) 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.

(8) Homoserine analogues in the following table were prepared by the methods of Example 1a, Example 1b or similar methods known in the art.

(9) TABLE-US-00001 Brief description of No. Homoserine analogue the preparation method Characterization data 1. 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) 3.74-3.55 (m, 6H), 2.47 (s, 2H), 2.19-2.09 (m, 1H), 1.96-1.82 (m, 1H). 2. 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) 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. 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) 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) 174.7, 67.5, 51.5, 42.1, 37.04, 21.5. 4. 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) 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. The alcohol in Example 1a was replaced with isobutanol. 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, DMSO-d.sub.6) 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) 175.1, 70.0, 51.5, 42.1, 37.1, 27.3, 18.8. 6. It was prepared according to a method similar to that disclosed in WO 2006117552 A1. 7. 0 It was prepared according to a method disclosed in WO 98/58256. 8. 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) 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) 170.7, 169.7, 61.0, 50.6, 25.2, 24.4, 22.5, 14.0. 9. 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) 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) 171.5, 166.8, 133.6, 131.6, 128.3, 127.5, 60.8, 50.3, 41.9, 33.3, 14.1. 10. 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) 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) 170.6, 142.7, 138.1, 129.4, 126.5, 60.9, 53.0, 41.0, 34.8, 20.9, 13.7. 11. 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) 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) 171.6, 169.6, 60.7, 49.6, 41.5, 33.7, 22.3, 14.0. 12. It was prepared according to a method disclosed in CN 110386882 A MS (ESI): m/z [M + H]+ calculated for C.sub.9H.sub.17ClNO.sub.4: 238.09; found: 238.1. .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 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. 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) 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) 172.0, 155.6, 78.4, 60.6, 51.1, 41.7, 33.4, 28.1, 14.0. 14. 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) 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) 167.5, 51.3, 42.3, 39.7, 33.4, 21.2, 21.1. 15. Compound 16-1 in Example 1b was replaced with 0 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) 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) 168.5, 51.4, 39.8, 39.5, 33.5, 30.2, 19.4, 13.0. 16. 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) 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) 168.5, 48.6, 39.8, 37.1, 35.9, 32.6. 17. It was prepare 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) 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) 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

(10) ##STR00043##

(11) 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 ml2), 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.).

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

(13) .sup.1H NMR (400 MHz, CDCl.sub.3) 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).

(14) .sup.13C NMR (100 MHz, CDCl.sub.3) 68.2, 24.6, 19.9, 10.2.

(15) .sup.31P NMR (160 MHz, CDCl.sub.3) 33.5.

(16) The following compounds were prepared according to a method similar to that described above.

(17) TABLE-US-00002 Difference as compared with the method in No. Alkyl phosphonite Example 2 Characterization data 1 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) 4.11 (dp, J = 9.6, 6.2 Hz, 2H), 1.18- 1.06 (m, 15H). .sup.13C NMR (100 MHz, CDCl.sub.3) 70.3, 24.7, 21.5. .sup.31P NMR (160 MHz, CDCl.sub.3) 30.1. 2 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) 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) 66.3, 33.5, 20.0, 19.0, 13.7. .sup.31P NMR (160 MHz, CDCl.sub.3) 28.7.

Example 3

(18) ##STR00046##

(19) 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)

(20) ##STR00047##
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 mL3). 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.

(21) 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.

(22) TABLE-US-00003 Compound of Compound of No. Formula (IIa) Formula (IV) Yield ee value 1. 76% 98% 2. 0 78.2% 98% 3. 65.1% 95% 4. 79.7% 98% 5. 48.4% 99% 6. 24.8% 65% 7. 38% 86% 8. 70.80% 96% 9. 34.1% 93% 10. 35% 97% 11. 19.4% 53% 12. 0 22% 91% 13. 43% 73% 14. 82% 97% 15. 74.5% 95%

Example 4

(23) ##STR00065##

(24) 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

(25) ##STR00066##
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 2h. The reaction was naturally cooled to room temperature, filtered with suction, and the filter cake was washed with chlorobenzene (2.5 L2). 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 10h, and at the same 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%).

(26) 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.