5-Aminovaleric acid → Methyl 5-aminopentanoate hydrochloride

Participants

Reaction Steps

Acetyl chloride (5 mL) was added into methanol (150 mL) to prepare hydrogen chloride in methanol solution, and 5-aminopentanoic acid (1 g) was added. The mixture was kept at the room temperature overnight, and evaporated to isolate methyl 5-aminopentanoate hydrochloride. A mixture of the methyl 5-aminopentanoate hydrochloride (251 mg), cinnamoic acid (74 mg), HBTU (168 mg), diisopropylethylamine (0.87 mL), and dimehylformamide (2 mL) was kept at the room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (20 mL), washed with water twice (10 mL each) followed by brine (10 mL), dried (Na2SO4), and evaporated to isolate (4-methoxycarbonyl)butyl cinnamamide (1, 100 mg). A mixture of (4-methoxycarbonyl)butyl cinnamamide (1, 100 mg), benzaldehyde phenylhydrazone (2, 113 mg), chloramine-T trihydrate (160 mg), and methanol (2 mL) were heated under refluxing for 22 hours. The reaction mixture was diluted with 50% ethyl acetate in n-hexanes (40 mL), filtered, and evaporated. The residue was purified by column chromatography (silica gel 20 g, eluent: 0 to 10% ethyl acetate gradient in hexanes) to isolate methyl 5-(1,3,5-triphenyl-4,5-dihydro-pyrazole-4-carbonyl) aminopentanoate (3, 13 mg) and methyl 5-(1,3,4-triphenyl-4,5-dihydro-pyrazole-5-carbonyl)aminopentanoate (4, 103 mg). Regiochemistry of each isomer was identified by 1H- and 13-C NMR chemical shifts of the CH adjacent to the amide carbonyl. 5-(1,3,5-Triphenyl-4,5-dihydro-pyrazole-4-carbonyl)aminopentanoic acid (5, FN1-9U) were obtained from 3 by a standard ester hydrolysis condition as shown in the preparation of FN1-2. MS: 464.9 (M+Na), 442.9 (M+H), 325.8, 297.9. 5-(1,3,4-Triphenyl-4,5-dihydro-pyrazole-5-carbonyl)aminopentanoic acid (6, FN1-9S) were obtained from 4 by a similar manner to the preparation of FN1-2. MS: 464.9 (M+Na), 442.9 (M+H), 325.8, 297.9.

Provenance & Evidence