Process of preparation of indoxacarb and its intermediates
AssigneeAdama Makhteshim Ltd.
InventorsEran FOGLER, Regev PARNES, Sanaa MUSA, Natalia STRIZHIVER, Chen VAZANA, Avi MONHAIT, Hagit FORCKOSH
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel di-imine, oxadiazepine and oxadiazine intermediates as key intermediates for preparation of oxadiazine insecticides, the processes of their preparation, purification and use in the preparation of final oxadiazine pesticides, in particular of indoxacarb. Telescopic process of preparation of arthropocidal oxadiazines, in particular indoxacarb is disclosed.
Claims45
A di-imine of formula I which is racemic or enantiomerically enriched at chiral center*:
- Wherein R1, R2 are independently hydrogen, C1-C4-alkyl
- R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4 alkoxy
- m=1-3
- n=1-3
A di-imine of formula I, which is racemic or enantiomerically enriched at chiral center*, wherein R1 is H, R2 is H, R3 is CO2Me, R4 is Cl, n is 1, m is 1:
A process for preparation of a di-imine of formula I which is racemic or enantiomerically enriched at chiral center*, comprising reaction of compound of formula II
- Wherein R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4 alkoxy
- m=1-3
- n=1-3
- with compound of formula III or/and compound of formula IIIa
- Wherein X1=O, +NL2X−, L is hydrogen, C1-C4 alkyl, X is halogen, R1, R2 are independently hydrogen, C1-C4-alkyl, in the presence of organic solvent and optionally, in the presence of catalyst.
A process for preparation of compound of formula Ia which is racemic or enantiomerically enriched at chiral center*
- comprising the reaction of compound of formula IIa,
- with formaldehyde, and/or with N,N-Dimethylmethyleneiminium chloride (CAS 30354-18-8) and/or with tetramethylmethanediamine in the presence of organic solvent selected from the group consisting of toluene, xylene, monochlorobenzene, dichlorobenzene, ethylbenzene, cyclopentylmethyl ether, methyl-tert-butyl ether, benzonitrile and mixtures thereof, optionally in the presence of ammonium salt.
A compound of formula V, which is racemic or enantiomerically enriched at chiral center*:
- Wherein R1, R2 is independently hydrogen, C1-C4-alkyl
- R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4alkoxy
- X2=OR1, N(R1)2
- m=1-3
- n=1-3
A compound of formula V, which is racemic or enantiomerically enriched at chiral center* wherein R1 is H, R2 is H, R3 is CO2Me, R4 is Cl, n is 1, m is 1, X2 is OH:
A process for preparation of compound of formula V, which is racemic or enantiomerically enriched at chiral center*,
- Wherein R1, R2 is independently hydrogen, C1-C4-alkyl
- R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4 alkoxy
- X2=OR1, N(R1)2
- m=1-3
- n=1-3
- comprising reaction of compound of formula I
- Wherein R1, R2 are independently hydrogen, C1-C4-alkyl
- R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4 alkoxy
- m=1-3
- n=1-3
- with compound of formula III or/and compound of formula IIIa
- Wherein X1=O, +NL2X−, L is hydrogen, C1-C4 alkyl, X is halogen, R1, R2 are independently hydrogen, C1-C4 alkyl, in the presence of organic solvent and, optionally, in the presence of catalyst.
A process of preparing of compound of formula Va, which is racemic or enantiomerically enriched at chiral center*,
- the process comprising the reaction of compound of formula Ia
- with formaldehyde in the presence of organic solvent, and optionally in the presence of catalyst.
A compound of formula VI, which is racemic or enantiomerically enriched at chiral center*:
- Wherein R1, R2=hydrogen, C1-C4-alkyl
- R3=C1-C4-alkoxycarbonyl, COOH
- R4=Halogen, C1-C4 alkyl, C1-C4 alkoxy
- m=1-3
- n=1-3
A compound of formula VIa, which is racemic or enantiomerically enriched at chiral center wherein R1 is H, R2 is H, R3 is CO2Me, R4 is Cl, n is 1, m is 1:
A process of preparing of compound of formula VI, which is racemic or enantiomerically enriched at chiral center*
- the process comprising the reaction of compound of formula I
- with a compound of formula V
- Wherein R1, R2 is independently hydrogen, C1-C4-alkyl
- R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4 alkoxy
- X2=OR1, N(R1)2
- m=1-3
- n=1-3
- in the presence of organic solvent and optionally, in the presence of catalyst.
A process of preparing of compound of formula VI which is racemic or enantiomerically enriched at chiral center*
- Wherein R1, R2=hydrogen, C1-C4-alkyl
- R3=C1-C4-alkoxycarbonyl, COOH
- R4=Halogen, C1-C4alkyl, C1-C4 alkoxy
- m=1-3
- n=1-3
- the process comprising the reaction of compound of formula V with compound of formula II
- Optionally, in the presence of compound of formula III or IIIa
- Wherein X1=O, +NL2X−, L is hydrogen, C1-C4 alkyl, X is halogen, R1, R2 is independently hydrogen, C1-C4-alkyl,
- in the presence of organic solvent and optionally, in the presence of catalyst.
A process of preparing of compound of formula VIa which is racemic or enantiomerically enriched at chiral center*
- the process comprising the reaction of compound of formula IIa
- with dimethylmethyleneammonium chloride in the presence of organic solvent and optionally, in the presence of catalyst.
A process of preparing of compound of formula VIa which is racemic or enantiomerically enriched at chiral center*
- the process comprising the reaction of compound of formula IIa
- with tetramethylmethanediamine in the presence of organic solvent and optionally in the presence of catalyst.
A process of preparing of compound of formula VIa which is racemic or enantiomerically enriched at chiral center*
- the process comprising the reaction of compound of formula Ia
- with formaldehyde optionally in the presence of organic solvent selected from the group consisting of toluene, xylene, monochlorobenzene, dichlorobenzene, ethylbenzene, cyclopentylmethyl ether, methyl-tert-butyl ether, benzonitrile and mixtures thereof.
A process for preparing of compound of formula IV which is racemic or enantiomerically enriched at chiral center*
- Wherein R1, R2=hydrogen, C1-C4-alkyl
- R3=C1-C4-alkoxycarbonyl, COOH
- R4=Halogen, C1-C4 alkyl, C1-C4 alkoxy
- R6=hydrogen, CO2Me, CO2(R′)
- X3=Halogen, OCF3, SCF3
- n=1-3;
- the process comprising the reaction of compound of formula I
- with a compound of formula VII:
- Wherein R6=hydrogen, CO2Me, CO2(R1)
- n=1-3
- X3=Halogen, OCF3, SCF3
- X4=Halogen, triflate, tosylate
- in the presence of organic solvent.
A process for preparation of compound of formula IVa which is racemic or enantiomerically enriched at chiral center*
- comprising the reaction of compound of formula Ia
- with a compound of formula VIIa
- in the presence of organic solvent.
A process for preparing of compound of formula IVa which is racemic or enantiomerically enriched at chiral center*
- the process comprising the reaction of compound of formula VIa
- with a compound of formula VIIa
- in the presence of organic solvent.
A process for preparing of compound of formula IVa which is racemic or enantiomerically enriched at chiral center*
- the process comprising the reaction of compound of formula Va
- with a compound of formula VIIa
- in the presence of organic solvent.
A process for preparation of compound of formula IV which is racemic or enantiomerically enriched at chiral center*
- Wherein R1, R2=hydrogen, C1-C4-alkyl
- R3=C1-C4-alkoxycarbonyl, COOH
- R4=Halogen, C1-C4 alkyl, C1-C4 alkoxy
- R6=hydrogen, CO2Me, CO2(R1)
- X3=Halogen, OCF3, SCF3
- n=1-3;
- comprising the reaction of at list one of the compounds of formula I, V and/or VI:
- Wherein R1, R2 is independently hydrogen, C1-C4-alkyl
- R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4alkoxy
- X2=OR1, N(R1)2
- m=1-3
- n=1-3
- Wherein R1, R2 are independently hydrogen, C1-C4-alkyl
- R3 is C1-C4-alkoxycarbonyl, COOH
- R4 is halogen, C1-C4 alkyl, C1-C4 alkoxy
- m=1-3
- n=1-3
- Wherein R1, R2=hydrogen, C1-C4-alkyl
- R3=C1-C4-alkoxycarbonyl, COOH
- R4=Halogen, C1-C4 alkyl, C1-C4 alkoxy
- m=1-3
- n=1-3
- with a compound of formula VII in the presence of organic solvent.
- Wherein R6=hydrogen, CO2Me, CO2(R1)
- n=1-3
- X3=Halogen, OCF3, SCF3
- X4=Halogen, triflate, tosylate
- in the presence of organic solvent.
A process for preparation of compound of formula IVa which is racemic or enantiomerically enriched at chiral center*
- comprising the reaction of at list one of the compounds of formula Ia, Va and/or Via
- with a compound of formula Vila
- in the presence of organic solvent.
Purification of compound of formula IV prepared according to any of the preceding claims by recrystallization from C1-C4 alcohol, optionally in the presence of water.
Purification of compound of formula IV prepared according to any of the preceding claims by recrystallization from isopropanol, optionally in the presence of water.
A compound of formula VIII (methyl 8-chloro-2-((methoxycarbonyl)(4-(trifluoromethoxy)phenyl)carbamoyl)-2,6-dihydro-3H-indeno[1,2-e][1,3,4]oxadiazepine-5a(5H)-carboxylate which is racemic or enantiomerically enriched at chiral center*:
A process for preparing of compound of formula VIII which is racemic or enantiomerically enriched at chiral center* according to the following scheme, comprising:
- a) reacting the mixture of methyl (S)-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate and (1H-Indene-2-carboxylic acid, 5-chloro-2,3-dihydro-1-oxo-, methyl ester) with hydrazine hydrate in the presence of methanol and acetic acid, b) reacting the mixture of methyl (S)-5-chloro-1-hydrazineylidene-2-hydroxy-2,3-dihydro-1H-indene-2-carboxylate and methyl 5-chloro-1-hydrazineylidene-2,3-dihydro-1H-indene-2-carboxylate prepared in a) with formaldehyde in the presence of pyridine hydrochloride, c) reacting the mixture of methyl (S)-5-chloro-2-hydroxy-1-(methylenehydrazineylidene)-2,3-dihydro-1H-indene-2-carboxylate and methyl 8-chloro-2,6-dihydro-3H-indeno[1,2-e][1,3,4]oxadiazepine-5a(5H)-carboxylate, prepared in step b) with methyl N-carbonochloridoyl-N-[4-(trifluoromethoxy)phenyl]carbamate:
A telescopic process of for preparation of compound of formula IV which is racemic or enantiomerically enriched at chiral center*
- Wherein R1, R2=hydrogen, C1-C4-alkyl
- R3=C1-C4-alkoxycarbonyl, COOH
- R4=Halogen, C1-C4 alkyl, C1-C4 alkoxy
- R6=hydrogen, CO2Me, CO2(R1)
- X3=Halogen, OCF3, SCF3
- n=1-3;
- comprising the steps of:
- a) preparation of compound I, or V, or VI or the mixture thereof;
- b) reaction of compound I, or V, or VI or the mixture thereof with compound of formula VII in the presence of organic solvent.
Dependencies are inferred from the claim text.