Ammonia → 4-BroMo-2,6-difluorobenzaMide, 96%

Temperature

0 °C

To a mixture of 4-bromo-2,6-difluorobenzoic acid (110 g) and triethylamine (65 g) in THF (1.5 L) at −50° C. was added ethylchloroformate (60 g) dropwise. After the addition, the reaction mixture was warmed to 0° C. and stirred at this temperature for 1 hour. Ammonia (2 L, 0.5 M in 1,4-dioxane) was added dropwise, and the reaction mixture was stirred overnight at room temperature. The mixture was concentrated, and the resulting residue was partitioned between 1N HCl aqueous solution (2 L) and CH2Cl2 (1 L). The resulting solid was filtered and washed with CH2Cl2 to afford the title compound (60 g). The organic layer of the filtrate was separated, dried over MgSO4, filtered and evaporated under vacuum to afford another portion of the title compound (50 g). 1H NMR (300 MHz, DMSO-d6): δ 7.56 (m, 2H), 7.91 (s, 1H), 8.15 (s, 1H).

1. additionAfter the addition
2. stirringthe reaction mixture was stirred overnight at room temperature
3. concentrationThe mixture was concentrated
4. customthe resulting residue was partitioned between 1N HCl aqueous solution (2 L) and CH2Cl2 (1 L)
5. filtrationThe resulting solid was filtered
6. washwashed with CH2Cl2

ORD record

ord-de999bd89cc74918a0f401ad232d6583

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697685B2