Ammonia → Methyl 2,4-diamino-3-fluoro-5-nitrobenzoate

To a stirred solution of methyl 4-amino-2,3-difluoro-5-nitrobenzoate (4) (33.0 g, 142.15 mmol) in 1,4-dioxane (165 mL, 1.93 moles), in a 250 mL glass pressure vessel, was added an aqueous solution of ammonia (39 g, 711 mmol, 42.9 mL, 16.5 M). The vessel was then heated in an immersion bath at a bath temperature between 79 and 105° C., for 80 minutes, over which time the internal pressure ranged between 0.2 and 2.7 bar. The pressure was then released slowly and the mixture was treated with water (330 mL, 10 vol). The resultant suspension was stirred for 20 minutes and then filtered under vacuum, and the solid was washed with water (33 mL, 1 vol). The solid was sucked dry, then dried in a vacuum oven at 50° C. to provide methyl 2,4-diamino-3-fluoro-5-nitrobenzoate (5) (32.6 g, 92% yield) as a yellow solid. 1H NMR (500 MHz, d6 DMSO) δ 3.83, (3H, s, OMe), 7.20 (2H, br, NH2), 7.37 (2H, br, NH2), 8.47 (1H, s, Ar—H). 13C NMR (100 MHz, d6 DMSO) δ 52 (CH3), 101 (C), 122 (C), 126 (CH), 134 (C), 137 (C), 142 (C), 166 (C═O). vmax/cm−1 3474, 3358, 1697, 1633, 1528, 1435, 1317, 1285.

1. temperatureThe vessel was then heated in an immersion bath at a bath temperature between 79 and 105° C.
2. filtrationfiltered under vacuum
3. washthe solid was washed with water (33 mL, 1 vol)
4. customThe solid was sucked dry
5. customdried in a vacuum oven at 50° C.

ORD record

ord-7228b022f40542a9843cf9f766408163

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08383832B2