2-Chloro-5-nitrobenzoic acid → Benzoyl chloride, 2-chloro-5-nitro-

Thionyl chloride (14 mL, 192 mmol) was added-dropwise to a solution of 2-chloro-5-nitrobenzoic acid (10 g, 49.6 mmol) in chloroform (150 mL) at 0° C. The mixture was heated to reflux for 4 h then cooled to r.t., concentrated in vacuo and dried under high vacuum to yield 2-chloro-5-nitrobenzoyl chloride (10 g, 91.7%) as a solid. Under nitrogen, triethylamine (19 mL, 136 mmol) was added slowly to a solution of aminoacetaldehyde dimethyl acetal (5.43 mL, 50.0 mmol) in dry DCM (20 mL) at 0° C. 2-Chloro-5-nitrobenzoyl chloride (10 g, 45.5 mmol) was slurried in dry DCM (30 mL) and added over a period of 30 minutes. The mixture was allowed to warm to r.t. and stirred overnight then partitioned between water and DCM. The organic phase was washed with saturated sodium bicarbonate solution, water and brine then dried over sodium sulfate and concentrated. The crude product was triturated with petroleum ether then diethyl ether and finally purified by column chromatography on silica gel (60-120 mesh) eluting with ethyl acetate/petroleum ether (2% to 40% gradient) to afford 2-chloro-N-(2,2-dimethoxy-ethyl)-5-nitro benzamide (8.3 g, 63%) as a yellow solid.

1. temperatureThe mixture was heated
2. temperatureto reflux for 4 h
3. concentrationconcentrated in vacuo
4. customdried under high vacuum

ORD record

ord-d1237eec92924d90996b8ebb92d23958

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604029B2