Triethylamine → Isopropyl 3-nitro-4-(3-(1-piperidinyl)anilino)benzoate

Participants

Reaction Conditions

Reaction Steps

To a mixture of isopropyl 4-chloro-3-nitrobenzoate (3.0 g, 12.3 mmol) and 2a (2.16 g, 12.3 mmol) in anhydrous NMP (5 ml) was added triethylamine (1.71 ml, 12.3 mmol) and the mixture was stirred at 80° C. under a stream of nitrogen overnight. The cooled mixture was partitioned between ethyl acetate and water. The organic phase was extracted with diluted hydrochloric acid (4M). The aqueous extract was rendered alkaline by addition of aqueous sodium hydroxide (12M) and extracted with ethyl acetate. This organic extract was dried over sodium sulfate and concentrated under reduced pressure. The residue was chromatographied on silica gel using a mixture of ethyl acetate and petroleum ether (1:1 v/v) as the eluent to yield isopropyl 3-nitro-4-(3-(1-piperidinyl)anilino)benzoate (2.55 g, 54%) as a red oil. This intermediate product was dissolved in ethanol (50 ml) hydrogenated at ambient pressure. The resulting diamine was treated with formic acid (25 ml) at 80° C. for 1 hour. The reaction mixture was poured into water (100 ml) and rendered alkaline by addition of aqueous sodium hydroxide (10M). The crude product was filtered off, washed with water and dried. Purification was achieved by treatment with activated carbon in refluxing 2-propanol followed by trituration with diethyl ether. Yield of 4e1: 1.27 g (53%). M.p. 160-161° C.

Provenance & Evidence