Acetic Acid → 4-{[(4-Chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

Add sodium triacetoxyborohydride (30.50 g, 144 mmol) to a stirred solution of 4-amino-1-N-Boc-piperidine (18.00 g, 89.9 mmol), 4-chloro-thiazole-5-carbaldehyde (13.09 g, 88.7 mmol), acetic acid (5.5 mL, 96.1 mmol), and 1,2-dichloroethane (350 mL). Stir the reaction for 18 hours at room temperature under nitrogen. Pour the reaction into 2N NaOH (400 mL) and extract with ethyl acetate (3×150 mL). Wash the ethyl acetate with brine (2×150 mL). Dry the ethyl acetate over sodium sulfate and then filter off the sodium sulfate. Concentrate on a rotary evaporator and purify the crude product by flash chromatography on silica gel eluting with 75% ethyl acetate/hexanes then with 100% ethyl acetate to yield 21.78 g (74%) of 4-{[(4-chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=332.1 (M+1); 1H NMR (CDCl3): δ=8.67 (s, 1H), 4.10-4.02 (m, 4H), 2.88-2.82 (m, 2H), 2.74-2.67 (m, 1H), 1.92-1.89 (m, 2H), 1.49 (s, 9H), 1.37-1.28 (m, 3H).

Provenance & Evidence