METHOD OF PREPARATION OF FLORASULAM
The present disclosure concerns a method for preparing florasulam which involves treating a solution of 2,6-difluoroaniline in 1,2-propylene glycol with: a) sulfonyl chloride III and then b) a base to provide, after workup and isolation, florasulam (I) in yields of about 65-85%. The treatment of 2,6-difluoroaniline with sulfonyl chloride III and the base are conducted by controlled additions.
1 . A method of preparing florasulam (compound I)
comprising:
a) adding sulfonyl chloride III
to 2,6-difluoroaniline to form a mixture; and
b) adding a base to the mixture formed in step a).
2 . The method of claim 1 , wherein the adding of sulfonyl chloride III is done by controlled addition.
3 . The method of claim 1 , wherein the adding of a base to the mixture formed in step a) is done by controlled addition.
4 . The method of claim 1 , further comprising combining the 2,6-difluoroaniline with a glycol solvent prior to adding the sulfonyl chloride III.
5 . The method of claim 4 , wherein the glycol solvent is 1,2-propylene glycol.
6 . The method of claim 1 , wherein the mole ratio of 2,6-difluoroaniline to sulfonyl chloride II is from about 1:1 to about 2:1.
7 . The method of claim 1 , wherein the mole ratio of the base to sulfonyl chloride II is from about 0.5:1 to about 2:1.
8 . The method of claim 1 , wherein the base is selected from a trialkylamine, or a heterocylic amine
9 . The method of claim 8 , wherein the trialkylamine is triethylamine.
10 . The method of claim 8 , wherein the heterocylic amine is pyridine.
11 . A method of preparing florasulam (compound I)
comprising:
a) controlled adding of sulfonyl chloride III
to 2,6-difluoroaniline to form a mixture; and
b) controlled adding of a base to the mixture formed in step a).
12 . The method of claim 11 , further comprising combining the 2,6-difluoroaniline with 1,2-propylene glycol prior to adding the sulfonyl chloride III.
13 . The method of claim 11 wherein the mole ratio of 2,6-difluoroaniline to sulfonyl chloride II is from about 1:1 to about 2:1.
14 . The method of claim 13 , wherein the mole ratio of the base to sulfonyl chloride II is from about 0.5:1 to about 2:1.
15 . The method of claim 11 , wherein the base is selected from triethylamine or pyridine.
16 . A method of preparing florasulam (compound I)
comprising:
a) adding sulfonyl chloride III
to 2,6-difluoroaniline while maintaining a temperature during the adding of 20-30° C. to form a mixture; and
b) adding a base to the mixture formed in step a) while maintaining the temperature during the adding of 20-30° C.
17 . The method of claim 16 , further comprising combining the 2,6-difluoroaniline with 1,2-propylene glycol prior to adding the sulfonyl chloride III.
18 . The method of claim 16 wherein the mole ratio of 2,6-difluoroaniline to sulfonyl chloride II is from about 1:1 to about 2:1.
19 . The method of claim 16 , wherein the mole ratio of the base to sulfonyl chloride II is from about 0.5:1 to about 2:1.
20 . The method of claim 16 , wherein the base is selected from triethylamine or pyridine.