Tert-butyl 5-fluoro-2-nitrophenylcarbamate → N2-(tert-Butoxycarbonyl)-4-fluoro-1,2-phenylenediamine

Temperature

50 °C

A slurry of Raney nickel (W.R. Grace 2800, 30.6 g calc. dry weight) was added to a 2-gallon Parr stirred pressure reactor containing THF (3 L). tert-Butyl 5-fluoro-2-nitrophenylcarbamate (102 g) was added. The vessel was sealed, purged, and pressurized to about 30 psig with hydrogen. The mixture was vigorously stirred at ambient temperature (20° C.) while hydrogen was supplied on-demand at 30 psig. After stirring for 16 h, the vessel was vented and purged with nitrogen. The product mixture was filtered to remove the catalyst using THF (1 L) to rinse the reactor and catalyst cake. The solvent was removed under vacuum. Heptane (510 mL) was added and the mixture was heated to 50° C. for 1 h, then cooled slowly to 0° C. The solids were filtered and washed with cold heptanes (100 mL) and dried under vacuum at 50° C. (76.7 g of product isolated, 87% pure, 73% yield).

1. customThe vessel was sealed
2. custompurged
3. stirringThe mixture was vigorously stirred at ambient temperature (20° C.) while hydrogen
4. stirringAfter stirring for 16 h
5. custompurged with nitrogen
6. filtrationThe product mixture was filtered
7. customto remove the catalyst
8. washto rinse the reactor and catalyst cake
9. customThe solvent was removed under vacuum
10. additionHeptane (510 mL) was added
11. temperaturecooled slowly to 0° C
12. filtrationThe solids were filtered
13. washwashed with cold heptanes (100 mL)
14. customdried under vacuum at 50° C.

ORD record

ord-8af694fa2ce14d7daa695f312f2ace09

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08748374B2