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) controlled adding of sulfonyl chloride III
to 2,6-difluoroaniline over a period of at least 1 hour while maintaining a temperature during the adding of 15° C. to 35° C. to form a mixture; and
b) controlled adding of a base to the mixture formed in step a) over a period of at least 0.5 hours while maintaining a temperature during the adding of 15° C. to 30° C.
2. The method of claim 1 , further comprising combining the 2,6-difluoroaniline with a glycol solvent prior to adding the sulfonyl chloride III.
3. The method of claim 2 , wherein the glycol solvent is 1,2-propylene glycol.
4. The method of claim 1 , wherein the mole ratio of 2,6-difluoroaniline to sulfonyl chloride III is from about 1:1 to about 2:1.
5. The method of claim 1 , wherein the mole ratio of the base to sulfonyl chloride III is from about 0.5:1 to about 2:1.
6. The method of claim 1 , wherein the base is selected from a trialkylamine, or a heterocylic amine.
7. The method of claim 6 , wherein the trialkylamine is triethylamine.
8. The method of claim 6 , wherein the heterocylic amine is pyridine.
9. A method of preparing florasulam (compound I)
comprising:
a) controlled adding of sulfonyl chloride III
to 2,6-difluoroaniline over a period of at least 1 hour while maintaining a temperature during the adding of 15° C. to 30° C. to form a mixture; and
b) controlled adding of a base to the mixture formed in step a) over a period of at least 0.5 hours while maintaining a temperature during the adding of 15° C. to 30° C.
10. The method of claim 9 , further comprising combining the 2,6-difluoroaniline with 1,2-propylene glycol prior to adding the sulfonyl chloride III.
11. The method of claim 9 wherein the mole ratio of 2,6-difluoroaniline to sulfonyl chloride III is from about 1:1 to about 2:1.
12. The method of claim 11 , wherein the mole ratio of the base to sulfonyl chloride III is from about 0.5:1 to about 2:1.
13. The method of claim 9 , wherein the base is selected from triethylamine or pyridine.
14. A method of preparing florasulam (compound I)
comprising:
a) controlled adding of sulfonyl chloride III
to 2,6-difluoroaniline over a period of at least 1 hour while maintaining a temperature during the adding of 20-25° C. to form a mixture; and
b) controlled adding of a base to the mixture formed in step a) over a period of at least 1 hour while maintaining the temperature during the adding of 20-25° C.
15. The method of claim 14 , further comprising combining the 2,6-difluoroaniline with 1,2-propylene glycol prior to adding the sulfonyl chloride III.
16. The method of claim 14 wherein the mole ratio of 2,6-difluoroaniline to sulfonyl chloride III is from about 1:1 to about 2:1.
17. The method of claim 14 , wherein the mole ratio of the base to sulfonyl chloride III is from about 0.5:1 to about 2:1.
18. The method of claim 14 , wherein the base is selected from triethylamine or pyridine.