Toluene → N-1,3-thiazol-2-ylpyrrolidine-1-carboxamide

Temperature

-60 °C

Thiazol-2-amine (7.01 g, 10.0 mmol) was dissolved into dichloromethane (700 mL) and cooled to −60° C. The resulting suspension was treated with 20% phosgene in toluene (54 mL, 103 mmol) over 5 minutes and stirred for 10 minutes more before the addition of diisopropylethylamine (24 mL, 138 mmol). After the mixture was stirred for another 20 minutes near −60° C., pyrrolidine (17.5 mL, 210 mmol) was added, and after a few minutes the cold bath was removed. The mixture was warmed to 10° C. over a period of more than an hour, and then was quenched with concentrated aqueous ammonium hydroxide (100 mL) and stirred thoroughly. The aqueous phase was separated and extracted with dichloromethane, and the combined organic phases were washed twice with water; each aqueous phase was back-extracted with dichloromethane. The combined organic phases were concentrated to a slurry and diluted with 2:1 hexanes/ethyl acetate (30 mL). The solids were collected by filtration, rinsed with more 2:1 hexanes/ethyl acetate, slurried and rinsed in 2:1 hexanes/dichloromethane, and dried under vacuum to give the title compound.

1. customafter a few minutes the cold bath was removed
2. temperatureThe mixture was warmed to 10° C. over a period of more than an hour
3. customwas quenched with concentrated aqueous ammonium hydroxide (100 mL)
4. stirringstirred thoroughly
5. customThe aqueous phase was separated
6. extractionextracted with dichloromethane
7. washthe combined organic phases were washed twice with water
8. extractioneach aqueous phase was back-extracted with dichloromethane
9. concentrationThe combined organic phases were concentrated to a slurry
10. additiondiluted with 2:1 hexanes/ethyl acetate (30 mL)
11. filtrationThe solids were collected by filtration
12. washrinsed with more 2:1 hexanes/ethyl acetate
13. washrinsed in 2:1 hexanes/dichloromethane
14. customdried under vacuum

ORD record

ord-ff30103855f24543b59057b82695d334

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383657B2