Preparation and use of 2-substituted-5-oxo-3-pyrazolidinecarboxylates
View Patent ↗A method is disclosed for preparing a 2-substituted-5-oxo-3-pyrazolidinecarboxylate compound of Formula I The method comprises contacting a succinic acid derivative of the formula R 1 OC(O)C(H)(X)C(R 2a )(R 2b )C(O)Y (i.e. Formula II) wherein X and Y are leaving groups and L, R 1 , R 2a and R 2b are as defined in the disclosure, with a substituted hydrazine of the formula LNHNH 2 (i.e. Formula III) in the presence of a suitable acid scavenger and solvent. Also disclosed is the preparation of compounds of Formula IV wherein X 1 , R 6 , R 7 , R 8a , R 8b , R 9 , and n are as defined in the disclosure. Also disclosed is a composition comprising on a weight basis about 20 to 99% of the compound of Formula II wherein R 1 , R 2a , R 2b , R 3 , R 4 and R 5 are as defined in the disclosure; X is Cl, Br or I; and Y is F, Cl, Br or I; provided that when R 2a and R 2b are each H, and X and Y are each Cl then R 1 is other than benzyl and when R 2a and R 2b are each phenyl, and X and Y are each Cl, then R 1 is other than methyl or ethyl. Also disclosed is a crystalline composition comprising at least about 90% by weight of the compound of the formula R 1 OC(O)C(H)(X)C(R 2a )(R 2b )CO 2 H (i.e. Formula VI) wherein R 2a and R 2b are H, X is Br and R 1 is methyl.
1. A composition comprising on a weight basis about 20 to 99% of the compound of Formula II
wherein
R 1 is an optionally substituted carbon moiety;
R 2a is H, OR 4 or an optionally substituted carbon moiety;
R 2b is H or an optionally substituted carbon moiety;
R 4 is an optionally substituted carbon moiety; and
X is Cl, Br or I; and
Y is F, Cl, Br or I;
provided that when R 2a and R 2b are each H, and X and Y are each Cl then R 1 is other than benzyl and when R 2a and R 2b are each phenyl, and X and Y are each Cl, then R 1 is other than methyl or ethyl.
2. The composition of claim 1 wherein R 1 is methyl;
R 2a and R 2b are H;
X is Br; and
Y is Cl.
3. The composition of claim 1 wherein R 1 is ethyl;
R 2a and R 2b are H;
X is Br; and
Y is Cl.
4. A method of making the composition of claim 1 wherein R 1 is C 1 -C 4 alkyl, R 2a is H, R 2b is H, X is Br and Y is Cl, comprising contacting a compound of Formula VI
with a reagent for converting carboxylic acids to acyl chlorides in a suitable solvent.
5. The method of claim 4 wherein the reagent for converting carboxylic acids to acyl chlorides is thionyl chloride.
6. The method of claim 4 wherein the suitable solvent is dichloromethane, 1,2-dichloroerhane, chlorobenzene, benzene or toluene.
7. The method of claim 6 wherein the suitable solvent is dichloromethane.
8. The method of claim 4 wherein R 1 is CH 3 .
9. The method of claim 8 wherein the compound of Formula VI is prepared by adding the monomethyl ester of maleic acid to hydrobomic acid in acetic acid.
10. A method for preparing a compound of Formula IIa
wherein
R 1 is C 1 -C 4 alkyl;
X is Br; and
Y is Cl
comprising:
contacting a compound of Formula VI
with a reagent for converting carboxylic acids to acyl chlorides in a suitable solvent.
11. The method of claim 10 wherein the reagent for converting carboxylic acids to acyl chlorides is thionyl chloride.
12. The method of claim 10 wherein the suitable solvent is dichloromethane, 1,2-dichloroethane, chlorobenzene, benzene or toluene.
13. The method of claim 12 wherein the suitable solvent is dichloromethane.
14. The method of claim 10 wherein R 1 is CH 3 .
15. The method of claim 14 wherein the compound of Formula VI is prepared by adding the monomethyl ester of maleic acid to hydrobromic acid in acetic acid.