反应详情

A solution of LiAlH4 (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, 1 eq.) 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), 1N 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/1% TEA/CH2Cl2 to give the title compound 4-aminomethyl-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (0.26 g, 0.625 mmol, 26%) as a colorless oil. 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).

1. temperatureheated to 30° C. for 0.5 h
2. temperatureThe reaction was cooled to room temperature
3. temperatureThe mixture was heated to 55° C.
4. temperatureAfter 5 h the reaction was cooled to room temperature
5. customquenched by careful addition of H2O (0.323 mL), 1N NaOH (0.646 mL) and H2O (0.97 mL)
6. additionThis mixture was diluted with CH2Cl2 (25 mL)
7. stirringstirred vigorously for 1 h
8. filtrationfiltered through a pad of celite®
9. washThe salts were washed with CH2Cl2 (5×25 mL)
10. concentrationthe combined washings were concentrated by rotary evaporation
11. customto give the crude product as a yellow solid (0.597 g) which
12. customwas purified by flash column chromatography
13. washby eluting with 1% MeOH/1% TEA/CH2Cl2