Sulfuric Acid → 4-Aminomethyl-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

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A solution of LiAH4 (8.5 mL of a 1.0M solution in THF, 8.5 mmol, 3.5 eq.) was cooled to 0° C. and concentrated H2SO4 (0.43 mL, 7.6 mmol, 3.2 eq) was added in a drop-wise fashion. The resulting white slurry was stirred at room temperature for 0.5 h then heated to 30° C. for 0.5 h. The reaction was cooled to room temperature and a solution of 4-cyano-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (1 g, 2.43 mmol) in THF (3 mL) was added over 0.25 h. The mixture was heated to 55° C. and monitored by TLC. After 5 h the reaction was cooled to room temperature and quenched by careful addition of H2O (0.323 mL), 1 N NaOH (0.646 mL) and H2O (0.97 mL). This mixture was diluted with CH2Cl2 (25 mL) and stirred vigorously for 1 h and then filtered through a pad of celite®. The salts were washed with CH2Cl2 (5×25 mL) and the combined washings were concentrated by rotary evaporation to give the crude product as a yellow solid (0.597 g) which was purified by flash column chromatography by eluting with 1% MeOH/CH2Cl2 (+1% TEA) to give 4-aminomethyl-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (0.26 g, 26%). 1H NMR (CDCl3): δ 7.81 (d, 2H), 7.17 (d, 2H), 3.82 (m, 2H), 3.145 (m, 2H), 2.86 (s, 2H), 2.24 (m, 2H), 1.80 (m, 2H), 1.65 (br.m, 2H), 1.56 (s, 9H).

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