1-Hydroxybenzotriazole → 4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

関与物質

反応手順

3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carboxylic acid (556 mg, 2.45 mmol, 1.0 eq) is added at room temperature to a stirred solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 2.45 mmol, 1.0 eq) in N,N-dimethylformamide (20 mL), followed by 1-hydroxybenzotriazole (421 mg, 2.69 mmol, 1.1 eq), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (550 mg, 2.81 mmol, 1.15 eq) and N,N-diisopropylethylamine (962 μL, 5.50 mmol, 2.25 eq). After 15 hours stirring at room temperature, solvent is evaporated and the residue is extracted with dichloromethane (3×30 mL) and water (30 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude product that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:3:0 to 0/9/1, v/v/v) to afford 4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester as a light yellow solid (621 mg, 62% yield).

情報源と証拠