Tert-Butyl nitrite → 4-(4-Ethoxycarbonyl-thiophen-2-yl)-piperidine-1-carboxylic acid t-butyl ester

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Reaction Steps

4-(5-Amino-4-ethoxycarbonyl-thiophen-2-yl)-piperidine-1-carboxylic acid butyl ester (13.4 g, 38 mmol) was added to t-butyl nitrite (56.4 mmol) and copper(II)chloride (38 mmol) in IMS (500 mL). The reaction was stirred for 1 hour then saturated aqueous ammonium chloride (70 mL) was added and the resulting mixture stirred for a further 15 minutes. The solution was filtered and the filtrate was evaporated under vacuum. The residue was then partitioned between DCM and water. The organic layer was separated and dried over magnesium sulphate, filtered and the solvent evaporated. The product was purified by column chromatography on silica, eluting with 0%-40% ethyl acetate in cyclohexane to give a clear oil (11.7 g). 1H NMR (400 MHz, CHCl3-d): δ 7.9 (s, 1H), 7.2 (s, 1H), 4.3 (q, 2H), 4.2 (m, 2H), 2.9-2.7 (m, 3H), 2.0 (m, 2H), 1.7 (m, 2H), 1.5 (s, 9H), 1.4 (t, 3H).

Provenance & Evidence