反应详情

温度

0 °C

Add 4-{[(4-chloro-thiazol-5-yl)methyl]-isobutyl-amino}-piperidine-1-carboxylic acid tert-butyl ester (23.49 g, 60.6 mmol) to dichloromethane (140 mL) and cool to 0° C. Slowly add trifluoroacetic acid (47.0 mL, 610 mmol) and stir for 15 minutes at 0° C. and three hours at room temperature. Cool the reaction to 0° C. and slowly add chilled 2 N NaOH (400 mL). Extract with ethyl acetate (3×200 mL), wash with 2 N NaOH (100 mL) and then with brine (100 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 1.2% concentrated ammonium hydroxide/12% ethanol/chloroform then with 2% concentrated ammonium hydroxide/20% ethanol/chloroform to yield 15.59 g (89%) of [(4-chloro-thiazol-5-yl)methyl]-isobutyl-piperidin-4-yl-amine: mass spectrum (ion spray): m/z=288.1 (M+1); 1H NMR (CDCl3): δ=8.63 (s, 1H), 3.80 (s, 2H), 3.17-3.14 (m, 2H), 2.59-2.47 (m, 3H), 2.32 (d, 2H), 1.79-1.65 (m, 4H), 1.50-1.40 (m, 2H), 0.91 (d, 6H).

1. temperatureCool
2. customthe reaction to 0° C.
3. additionslowly add
4. extractionExtract with ethyl acetate (3×200 mL)
5. washwash with 2 N NaOH (100 mL)
6. dry with materialDry the ethyl acetate over sodium sulfate
7. filtrationfilter off the sodium sulfate
8. concentrationConcentrate on a rotary evaporator
9. custompurify the crude product by flash chromatography on silica gel eluting with 1.2% concentrated ammonium hydroxide/12% ethanol/chloroform