Sodium Carbonate → 4-Nitrophenyl 2-chloro-3-fluorobenzylcarbamate

Temperature

0 °C

A 5 liter 3-neck RBF was charged with 4-nitrophenylchloroformate (126.3 g, 627 mmol), DCM (3000 mL), under N2 atm and chilled in a 0° C. ice bath. A solution of 2-chloro,3-fluorobenzylamine (100.0 g, 627 mmol) followed by solid Sodium Carbonate (155.0 g, 1460 mmol) was quickly added in one portion into the reaction solution. The reaction mixture was stirred at 0° C. for 1 h and an LC/MS was taken to confirm consumption of the starting material and presence of the nitrophenyl intermediate. The reaction mixture was allowed to warm to room temperature and stirred for approximately 2 h. The mixture was filtered, and the filtrate was concentrated to give a white solid. The solid was redissolved with 600 ml of DCM and heated to 40° C. until all of the material went into solution. The solution was chilled in a 0° C. ice bath to form crystals. The crystals were collected and dried under vacuum to give 4-nitrophenyl 2-chloro-3-fluorobenzylcarbamate. (150 g, 75%).

1. additionwas quickly added in one portion into the reaction solution
2. customconsumption of the starting material and presence of the nitrophenyl intermediate
3. temperatureto warm to room temperature
4. stirringstirred for approximately 2 h
5. filtrationThe mixture was filtered
6. concentrationthe filtrate was concentrated
7. customto give a white solid
8. temperatureheated to 40° C. until all of the material
9. temperatureThe solution was chilled in a 0° C. ice bath
10. customto form crystals
11. customThe crystals were collected
12. customdried under vacuum

ORD record

ord-5f82b3fc56b24c88ac027fc1fe2d5655

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759374B2