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

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Reaction Steps

Add sodium triacetoxyborohydride (24.00 g, 113 mmol) to a stirred solution of 4-{[(4-chloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (21.78 g, 65.6 mmol), isobutyraldehyde (9.0 mL, 99.1 mmol), acetic acid (4.0 mL, 69.9 mmol), and 1,2-dichloroethane (260 mL). Stir the reaction for 18 hours at room temperature under nitrogen. Pour the reaction into 2N NaOH (300 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 25% ethyl acetate/hexanes to yield 24.67 g (97%) of 4-{[(4-chloro-thiazol-5-yl)methyl]-isobutyl-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=388.2 (M+1); 1H NMR (CDCl3): δ=8.65 (s, 1H), 4.21 (br s, 2H), 3.80 (s, 2H), 2.63-2.56 (m, 3H), 2.29 (d, 2H), 1.77-1.65 (m, 3H), 1.50-1.41 (m, 11H), 0.92 (d, 6H).

Provenance & Evidence