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). νmax/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-eca9425080bc468b8203bc4f3c0bf159

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501956B2