Stereoselective process to obtain (Z)-5-cyclyloxy-2-[(E)-methoxyimino]-3-methyl-pent-3-enic acid methyl amides using E,Z-isomer mixture of and intermediates thereof

Abstract

The present invention relates to a process for preparation of intermediates (Z,2E)-5-hydroxy-2-methoxyimino-N-methyl-pent-3-enamides from 4-substituted 5-meth-oxyimino-2H-pyran-6-ones and their processing for example to (Z)-5-cyclyloxy-2-[(E)-methoxyimino]-3-methyl-pent-3-enic acid methyl amides. The invention also relates to a process for preparation of 4-substituted 5-imino-2H-pyran-6-ones and to novel intermediates for the preparation of fungicidal (Z)-5-cyclyloxy-2-[(E)-methoxyimino]-3-methyl-pent-3-enic acid methyl amides.

Claims

1. A process for preparing compounds of formula I ##STR00030## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; Y is hydrogen, C.sub.1-C.sub.4-alkoxy, C.sub.2-C.sub.4-alkenyl or benzyl; and wherein the CH.sub.2OH group and the C(NOCH.sub.3)C(O)NYCH.sub.3 group are on the same side of the CC double bond between the carbon atoms depicted with the numbers 3 and 4 (Z-configuration), and wherein the OCH.sub.3 group and the C(O)NYCH.sub.3 group are on the opposite side of the CN double bond between the carbon atom depicted with number 2 and the neighbouring nitrogen atom (E-configuration); the process comprising: reacting a compound of formula II ##STR00031## wherein R is as defined above; with a compound of formula III ##STR00032## wherein Y is as defined above.

2. The process as claimed in claim 1, wherein a mixture of the E/Z-isomers of compounds of formula II is used, wherein said mixture comprises an E/Z-isomer ratio of from 0.1:1 to 10:1.

3. The process as claimed in claim 1, wherein R is C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-halogenalkyl.

4. The process as claimed in claim 3, wherein R is methyl of CF.sub.3.

5. The process as claimed in claim 1, wherein Y is allyl (prop-2-enyl), benzyl, methoxy or hydrogen.

6. The process as claimed in claim 5, wherein Y is hydrogen.

7. The process as claimed in claim 1, additionally comprising treating the compound I with a halogenating agent, n C.sub.1-C.sub.6-alkylsulfonyloxy halide, wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 halogen substituents, or phenylsulfonyl halide, wherein phenyl is unsubstituted or is substituted by 1, 2, 3, 4 or 5 substituents selected from halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-haloalkoxy and Cyclopropyl, to yield a compound of formula IV ##STR00033## wherein LG is a leaving group selected from halogen, C.sub.1-C.sub.6-alkylsulfonyloxy, wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 halogen substituents, and phenylsulfonyloxy, wherein phenyl is unsubstituted or is substituted by 1, 2, 3, 4 or 5 substituents selected from halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-haloalkoxy and cyclopropyl.

8. The process as claimed in claim 7, wherein LG is halogen and the halogenating agent is thionyl halide or phosphoryl halide.

9. The process as claimed in claim 7, additionally comprising treating the compound IV with a hydroxyl compound of formula V
R.sup.3OHV, wherein R.sup.3 is phenyl or a 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocyclyl wherein the ring member atoms of the heterocyclyl include besides carbon atoms 1, 2, 3 or 4 heteroatoms selected from the group of N, O and S; wherein the cyclic groups R.sup.3 may carry 1, 2, 3, 4 or up to the maximum possible number of identical or different groups R.sup.b which independently of one another are selected from: R.sup.b, which may be the same or different to any other R.sup.b, is amino, halogen, hydroxyl, oxo, nitro, CN, carboxyl, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkenyl, C.sub.2-C.sub.6-alkenyloxy, C.sub.3-C.sub.6-alkynyloxy, C.sub.1-C.sub.6-alkoxyimino-C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.6-alkenyloxyimino-C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.6-alkynyloxyimino-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylamino, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-alkylcarbonyloxy, phenyl, naphthyl or a 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocyclyl which, in addition to carbon atoms, contains one to four heteroatoms from the group consisting of N, O and S as ring members; and wherein the aforementioned phenyl and heterocyclyl groups R.sup.b are attached via a direct bond, an oxygen or sulfur atom, and two radicals R.sup.b that are bound to adjacent ring member atoms of the cyclic group R.sup.3 may form together with said ring member atoms a fused 5-, 6- or 7-membered saturated, partially unsaturated or aromatic cycle, which may be a carbocycle or heterocycle, wherein the ring member atoms of the heterocycle include besides carbon atoms 1, 2, 3 or 4 heteroatoms selected from the group of N, O and S, and where the aliphatic or cyclic groups R.sup.b for their part may carry 1, 2, 3 or up to the maximum possible number of identical or different groups R.sup.c: R.sup.c, which may be the same or different to any other R.sup.c, is halogen, hydroxyl, nitro, CN, carboxyl, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.8-alkynyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.1-C.sub.6-alkoxyimino-C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.6-alkenyloxyimino-C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.6-alkynyloxyimino-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.6-alkoxyimino-, C.sub.2-C.sub.6-alkenyloxyimino-, C.sub.2-C.sub.6-alkynyloxyimino-, C.sub.2-C.sub.6-haloalkenyloxyimino-, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkenyl, phenyl or a 5-membered saturated, partially unsaturated or aromatic heterocyclyl which, in addition to carbon atoms, contains one to three heteroatoms from the group consisting of N, O and S as ring members; wherein the aforementioned cyclic groups R.sup.c are attached via a direct bond, an oxygen or sulfur atom, and where the aliphatic or cyclic groups R.sup.c for their part may carry 1, 2, 3 or up to the maximum possible number of identical or different groups R.sup.d: R.sup.d, which may be the same or different to any other R.sup.d, is halogen, C.sub.1-C.sub.4-alkyl or C.sub.1-C.sub.4-haloalkyl; or R.sup.3 is CR.sup.ANOR.sup.B, wherein R.sup.A is amino, hydroxyl, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-halo-alkyl, C.sub.1-C.sub.4-alkoxy, C.sub.1-C.sub.4-haloalkoxy, C.sub.3-C.sub.6-cycloalkyl, C.sub.3-C.sub.6-cycloalkenyl, C.sub.2-C.sub.6-alkenyloxy, C.sub.3-C.sub.6-alkynyloxy, C.sub.1-C.sub.4-alkoxyimino-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkylamino, C.sub.1-C.sub.4-alkoxycarbonyl, C.sub.1-C.sub.4-alkylcarbonyloxy, phenyl, phenyl-C.sub.1-C.sub.4-alkyl, naphthyl or a 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocyclyl or which, in addition to carbon atoms, contains one to four heteroatoms from the group consisting of O, N and S as ring members; and wherein the aforementioned cyclic R.sup.A are attached via a direct bond, an oxygen or sulfur atom; R.sup.B is C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.4-alkynyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cyclo-alkyl, C.sub.3-C.sub.6-cycloalkenyl, C.sub.1-C.sub.4-alkoxyimino-C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-alkoxy-carbonyl, phenyl, phenyl-C.sub.1-C.sub.4-alkyl, naphthyl or a 3- to 10-membered saturated, partially unsaturated or aromatic mono- or bicyclic heterocyclyl or which, in addition to carbon atoms, contains one to four heteroatoms from the group consisting of O, N and S as ring members; where the aliphatic or cyclic groups R.sup.A and/or R.sup.B for their part may carry 1, 2, 3 or up to the maximum possible number of identical or different groups R.sup.e: R.sup.e, which may be the same or different to any other R.sup.e, is halogen, hydroxyl, nitro, CN, carboxyl, C.sub.1-C.sub.4-alkyl, C.sub.2-C.sub.4-alkenyl, C.sub.2-C.sub.8-alkynyl, C.sub.1-C.sub.4-haloalkyl, C.sub.1-C.sub.4-alkoxy or C.sub.1-C.sub.4-haloalkoxy; to yield a (Z,2E)-5-cyclyloxy-2-methoxyimino-N-substituted-pent-3-enamide of formula VI.

10. Compounds of formula I and compounds of IV ##STR00034## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; Y is hydrogen, C.sub.1-C.sub.4-alkoxy, C.sub.2-C.sub.4-alkenyl or benzyl; and wherein the CH.sub.2OH group and the C(NOCH.sub.3)C(O)NYCH.sub.3 group are on the same side of the CC double bond between the carbon atoms depicted with the numbers 3 and 4 (Z-configuration), and wherein the OCH.sub.3 group and the C(O)NYCH.sub.3 group are on the opposite side of the CN double bond between the carbon atom depicted with number 2 and the neighbouring nitrogen atom (E-configuration); and for compounds of formula IV, in addition: LG is a leaving group selected from halogen, C.sub.1-C.sub.6-alkylsulfonyloxy, wherein alkyl is unsubstituted or substituted by 1, 2, 3, 4 or 5 halogen substituents, and phenylsulfonyloxy, wherein phenyl is unsubstituted or is substituted by 1, 2, 3, 4 or 5 substituents selected from halogen, C.sub.1-C.sub.6-alkyl, C.sub.1-C.sub.6-haloalkyl, C.sub.1-C.sub.6-haloalkoxy and cyclopropyl.

11. Compounds of formula II ##STR00035## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl.

12. A process for preparing 5-methoxyimino-2H-pyran-6-one compounds of formula II ##STR00036## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; the process comprising: a) reacting a compound of formula VII ##STR00037## wherein R is as defined above; with a free-radical halogenating agent in an organic solvent to obtain intermediate compounds VIII ##STR00038## wherein Hal is halogen and R is as defined above; and b) after the first reaction step, treating the reaction mixture of step a) or compounds VIII with at least one base to obtain compounds II.

13. A process for preparing compounds of formula VII ##STR00039## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; the process comprising: a) reacting a compound of formula VII ##STR00040## wherein R is defined as above; with a nitrite in presence of Ag.sub.2O; and b) after the first reaction step, treating the reaction mixture of step a) with at least one alkylating agent selected from iodomethane, chloromethane, bromomethane or dimethyl sulfate, to obtain compounds VII.

14. A process for preparing compounds of formula VII ##STR00041## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; the process comprising: a) reacting a compound of formula VII ##STR00042## wherein R is defined as above; with a nitrite in presence of at least one base; and b) after the first reaction step, treating the reaction mixture of step a) with at least one alkylating agent selected from iodomethane, chloromethane, bromomethane or dimethyl sulfate, to obtain a mixture of compounds VII and compounds VIIb ##STR00043## wherein R is defined as above; and c) after the second reaction step, treating the reaction mixture of step b) or compounds VIIb with methoxyamine or methoxyamine halogenide to obtain compounds VII.

15. The process of claim 1, wherein the compound of formula II ##STR00044## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cyclo-alkyl-C.sub.1-C.sub.4-alkyl; is prepared by: a) reacting a compound of formula VII ##STR00045## wherein R is as defined above; with a free-radical halogenating agent in an organic solvent to obtain intermediate compounds VIII ##STR00046## wherein Hal is halogen and R is as defined above; and b) after the first reaction step, treating the reaction mixture of step a) or compounds VIII with at least one base to obtain compounds II.

16. The process of claim 15, wherein the compound of formula VII ##STR00047## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; is prepared by: a) reacting a compound of formula IX ##STR00048## wherein R is defined as above; with a nitrite in presence of Ag.sub.2O; and b) after the first reaction step, treating the reaction mixture of step a) with at least one alkylating agent selected from iodomethane, chloromethane, bromomethane or dimethyl sulfate, to obtain compounds VII.

17. The process of claim 15, wherein the compound of formula VII ##STR00049## wherein R is C.sub.1-C.sub.4-alkyl, C.sub.1-C.sub.4-haloalkyl, C.sub.3-C.sub.6-cycloalkyl or C.sub.3-C.sub.6-cycloalkyl-C.sub.1-C.sub.4-alkyl; is prepared by: a) reacting a compound of formula IX ##STR00050## wherein R is defined as above; with a nitrite in presence of at least one base; and b) after the first reaction step, treating the reaction mixture of step a) with at least one alkylating agent selected from iodomethane, chloromethane, bromomethane or dimethyl sulfate, to obtain a mixture of compounds VII and compounds VIIb ##STR00051## wherein R is defined as above; and c) after the second reaction step, treating the reaction mixture of step b) or compounds VIIb with methoxyamine or methoxyamine halogenide to obtain compounds VII.

Description

(1) The invention is illustrated by the following examples:

1. (3E,Z)-3-methoxyimino-4-methyl-tetrahydropyran-2-one

(2) ##STR00019##

(3) A solution of 500.0 g (4.3 mol) -methyl--valerolactone in 1500 ml toluene was treated with 1084.29 g (10.51 mol) tert-butylnitrite. To this mixture was added 737.32 g (6.57 mmol) potassium tert-butoxide (KOtBu) carefully in small portions over 60 min with stirring at 35 C. After 2 h at 40 C. iodomethane (1865.3 g, 13.11 mol) was added dropwise. The resulting mixture was stirred at about 23 C. overnight and quenched with cold 10% aqueous NaH.sub.2PO.sub.4 (10 L) and 74 ml of 12 N HCl (pH 5), then extracted with MTBE. The extracts were washed with 10% aqueous NaH.sub.2PO.sub.4, dried over anhydrous Na.sub.2SO.sub.4 and evaporated under vacuum. The residue (495 g) was chromatographed on silica gel using a gradient of 1:1 cyclohexane-MTBE to obtain 237 g (34.5%) product as an E,Z isomer mixture and 56.4 g (8.2%) of the N-alkylated nitrone.

(4) VII.1: .sup.1H-NMR (CDCl.sub.3): =1.2 (d); 1.7 (m); 2.2 (m); 3.3 (m); 4.1 (s); 4.23 (m); 4.5 (m);

(5) VIIb.1: .sup.1H-NMR (CDCl.sub.3): =1.2 (d); 1.7 (m); 2.2 (m); 3.4 (m); 4.2 (s); 4.23 (m); 4.4 (m).

1.1 (3E,Z)-3-methoxyimino-4-methyl-tetrahydropyran-2-one from nitrone

(6) ##STR00020##

(7) A solution of 56.35 g (358 mmol) nitrone (see byproduct of Ex. 1) in 400 ml DMF was treated with 59.89 g (717 mmol) CH.sub.3ONH.sub.2.HCl and the resulting mixture was stirred at 60 C. for 3 h, quenched with cold 10% aqueous NaH.sub.2PO.sub.4 and extracted with MTBE. The extracts were washed with saturated brine, dried over anhydrous Na.sub.2SO.sub.4 and evaporated under vacuum. The residue was chromatographed on silica gel using a gradient of 1:1 cyclohexane-MTBE to obtain 45 g (80%) product.

(8) VII.1: .sup.1H-NMR (CDCl.sub.3): =1.2 (d); 1.7 (m); 2.2 (m); 3.3 (m); 4.1 (s); 4.23 (m); 4.5 (m).

2. (3E,2)-4-bromo-3-methoxyimino-4-methyl-tetrahydropyran-2-one

(9) ##STR00021##

(10) In 500 ml CCl.sub.4 5.64 g (35.6 mmol) (3E,Z)-3-methoxyimino-4-methyl-tetrahydropyran-2-one (see Ex. 1) and 6.98 g (39.1 mmol) NBS were dissolved and a small amount of dibenzoyl peroxide was added and the mixture was refluxed for 1.5 h. The mixture was allowed to cool to about 23 C. and was filtered through a sintered glass plug of silica gel. The filtrate was evaporated in vacuo and the residue (8.72 g) was chromatographed on silica gel using cyclohexane-MTBE.

(11) Yield 6.72 g (79.8%) oil as a 82:18 E,Z-isomer mixture.

(12) .sup.1H-NMR (CDCl.sub.3): =2.1 (s); 2.4 (m); 4.22 (s); 4.4 (m); 4.78 (m).

3. (5E,Z)-5-methoxyimino-4-methyl-2H-pyran-6-one

(13) ##STR00022##

(14) A solution of 0.5 g (2.1 mmol) (3E,Z)-4-bromo-3-methoxyimino-4-methyl-tetrahydropyran-2-one (see Ex. 2) in 10 ml DMF was treated with 0.78 g (10 mmol) lithium carbonate and stirred for 2 h at 45 C. for and then at 60 C. until reaction completion was confirmed by HPLC analysis (approx. 1 h). The resulting mixture was partitioned between MTBE and 10% aqueous NaH.sub.2PO.sub.4 and of 12 N HCl (1.5 ml). The aqueous layer was extracted with MTBE and the combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 to afford 0.26 g as an E,Z-isomer mixture.

(15) (Z)-Isomer: .sup.1H-NMR (CDCl.sub.3): =1.97 (s); 4.13 (s); 4.97 (s); 6.00 (t).

(16) (E)-Isomer: .sup.1H-NMR (CDCl.sub.3): =2.20 (s); 4.10 (s); 4.90 (s); 6.00 (t).

4. (Z,2E)-5-hydroxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide

(17) ##STR00023##

(18) A solution of 2.55 g (16.4 mmol) (5E,Z)-5-methoxyimino-4-methyl-2H-pyran-6-one (see Ex. 3) in 20 ml THF was treated with 2.2 g (131 mmol) 40% aqueous methylamine and stirred at about 23 C. overnight. After removal of the solvents in vacuo the residue was chromatographed on silica gel using cyclohexane-MTBE. Yield 2.26 g (74%) as pure Z,2E-isomer. .sup.1H-NMR (CDCl.sub.3): =1.86 (s); 2.90 (d); 3.80 (d); 4.0 (s); 5.93 (t); 6.80 (broad).

5. (Z,2E)-5-hydroxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide

(19) ##STR00024##

(20) 3.93 g (25 mmol) (3E,Z)-3-methoxyimino-4-methyl-tetrahydropyran-2-one (see Ex. 1) and 4.89 g (27.5 mmol) NBS were dissolved in 150 ml ethyl acetate, a small amount of dibenzoyl peroxide (0.81 g) was added and the mixture was refluxed at about 65 C. for 1.5 h. The mixture was allowed to cool to about 23 C. and 100 ml of DMF was added, treated with 11 g (150 mmol) LiCO.sub.3 and stirred for 3 h at about 65 C. until reaction completion was confirmed by HPLC analysis. The mixture was cooled down to about 23 C., it was filtered and washed with ethyl acetate. The organic layer was washed three times with 30% solution of LiCl in water (3100 ml). The LiCl phase was extracted twice with ethyl acetate and the combined organic layers were dried over anhydrous Na.sub.2SO.sub.4 and concentrated under vacuum at about 30 C. The residue (4.9 g) was diluted with 45 ml THF followed by 40% aqueous methylamine (30 ml) and the mixture stirred for 90 min at 50 C.

(21) The reaction mixture was concentrated under vacuum to the volume of 25 ml, saturated with solid NaCl and extracted four times with ethyl acetate. The combined organic layers were dried over sodium sulfate, concentrated under vacuum and chromatographed on silica gel using ethyl acetate to obtain 2.1 g product as Z,2E-isomer (>95%) as an oil that crystallized upon standing.

(22) .sup.1H-NMR (CDCl.sub.3): =1.86 (s); 2.90 (d); 3.80 (d); 4.0 (s); 5.93 (t); 6.80 (broad).

6. (Z,2E)-5-chloro-2-methoxyimino-N,3-dimethyl-pent-3-enamide

(23) ##STR00025##

(24) 2.25 g (12 mmol) (Z,2E)-5-hydroxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide (see Ex. 5) have been dissolved in 50 ml dichloromethane. 1.83 g (18.1 mmol) triethylamine and 3.45 g (28.9 mmol) thionyl chloride dissolved in dichloromethane have been added with stirring at room temperature. After stirring overnight at about 23 C. 50% of the solvents have been removed in vacuo, the residue was diluted with MTBE before careful addition of aqueous NaHCO.sub.3. The precipitated salt was collected and washed with MTBE. The aqueous layer was extracted with MTBE and the combined organic layers were washed with saturated NaHCO.sub.3 and water and dried over anhydrous Na.sub.2SO.sub.4. Yield 2.47 g (85.3%), mp. 62 C.

(25) .sup.1H-NMR (CDCl.sub.3): =1.93 (s); 2.92 (d); 3.8 (d); 4.0 (s); 5.80 (t); 6.7 (broad).

7. (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide

(26) ##STR00026##

(27) 480 mg (2.4 mmol) (Z,2E)-5-chloro-2-methoxyimino-N,3-dimethyl-pent-3-enamide (see Ex. 6) and 500 mg (2.44 mmol) 1-(4-chlorophenyl)pyrazol-3-ol have been dissolved in 10 ml DMF. 680 mg (4.8 mmol) K.sub.2CO.sub.3 and 20 mg KI have been added with stirring for 2 h at 60 C. and then overnight at about 23 C. The reaction mixture was diluted with water, extracted with MTBE, the combined extracts were washed with water once and dried over anhydrous Na.sub.2SO.sub.4. After removal of the solvents in vacuo and the residue (0.71 g) chromatographed on silica gel using cyclohexane-MTBE to afford a yellow oil that crystallized upon standing: 460 mg (51.9%). mp: 126-128 C.

8. Comparative example for preparation of 5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-meth-oxyimino-N,3-dimethyl-pent-3-enamide (Compound IV from Ex. 7) in analogy to method described in WO 2013/092224

8a. 2-[1-(4-chlorophenyl)pyrazol-3-yl]oxyacetaldehyde

(28) ##STR00027##

(29) 4.86 g (15.63 mmol) 1-(4-chlorophenyl)-3-(2,2-diethoxy)pyrazol was treated with 150 ml 1 N hydrochloric acid solution in diethyl ether and stirred at about 23 C. overnight until reaction completion was confirmed by HPLC analysis. The reaction mixture was concentrated under vacuum, diethyl ether was added, washed with NaHCO.sub.3 solution and brine, dried over anhydrous Na.sub.2SO.sub.4 and concentrated under vacuum at about 29 C. to yield the title compound (3.8 g) that was used without further purification.

8b. Methyl-5-[-(1-(4-chlorophenyl)pyrazol-3-yl]oxy-2methoxyimino-3-methyl-pent-3-enoate

(30) ##STR00028##

(31) To 3.8 g 2-[1-(4-chlorophenyl)pyrazol-3-yl]oxyacetaldehyde in 90 ml THF 3.16 g (12.5 mmol) methyl (2Z)-3-dimethoxyphosphoryl-2-methoxyimino-butenoate (U.S. Pat. No. 5,346,898) was added, followed by 1.6 g (15 mmol) potassium tert-butylate in 30 ml THF. The reaction mixture was stirred at about 23 C. overnight and then concentrated. The residue was dissolved in MTBE, washed three times with water, dried over anhydrous Na.sub.2SO.sub.4, concentrated under vacuum and chromatographed on silica gel using a gradient of 3:1 heptane-MTBE to obtain 0.86 g product.

8c. 5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide

(32) ##STR00029##

(33) To 0.86 g methyl 5-[1-(1-(4-chlorophenyl)pyrazol-3-yl]oxy-2methoxyimino-3-methyl-pent-3-enoate in 20 ml THF was added 9.1 g 30% methylamine in THF and stirred at 55 C. After 8 h additional 20 ml 30% methylamine in THF was added and this process repeated after 6 h. The reaction mixture was concentrated under vacuum. The residue was dissolved in 200 ml MTBE, washed twice with brine, dried over anhydrous Na.sub.2SO.sub.4 and concentrated under vacuum. The residue was chromatographed on silica gel using a gradient of 1:1 heptane-MTBE to obtain:

(34) 34 mg of the desired isomer (Z,2E)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide

(35) .sup.1H-NMR (CDCl.sub.3): =1.98 (s); 2.68 (d); 3.98 (s); 4.92 (d); 5.9 (m, 2H); 5.9 (m); 6.9 (broad); 7.23 (s); 7.38 (m); 7.5 (m); 7.7 (s).

(36) 28 mg of the undesired isomer (E,2Z)-5-[1-(4-chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino-N,3-dimethyl-pent-3-enamide

(37) .sup.1H-NMR (CDCl.sub.3): =1.95 (s); 2.95 (d); 3.98 (s); 4.98 (d); 5.0 (d); 5.9 (m); 6.1 (m); 7.23 (s); 7.4 (m); 7.44 (m); 7.7 (s).

(38) Thus, the comparative example 8 provided a stereoselectivity of 34 mg to 28 mg which corresponds to a ratio of about 1.2:1 (ratio of the desired (Z,2E)-isomer of versus the sum of the corresponding (E,2E)-, (E,2Z)- and (Z,2Z)-isomers).