反应详情

Add over 30 min, at room temperature, a solution of LiAlH4 in diethyl ether (1M, 72.5 mL) to a solution of 4-[4-(6-fluoro-benzo[b]thiophen-3-yl)-[1,4]diazapan-1-yl]butyronitrile (Example 5) (11.5 g, 36.2 mmol) in dry diethyl ether (200 mL). Heat the solution to reflux for 5 h. After that time, allow the solution to cool to room temperature and carefully quench the reaction with water and aqueous sodium hydroxide solution. Separate the phases, and re-extract the aqueous phase with EtOAc. Dry the combined organic phases over MgSO4 and remove the solvent under vacuum. Purify the crude product by column chromatography (CH2Cl2/MeOH/NH4OH 9:2:0.25) to obtain 8.9 g of a colorless oil LC/MS, (LiChrospher 5μ, RP-18, 250 mm CH3CN/Water(0.05% TFA)-gradient 2%→98% (20 min), Flow: 0.75 mL/min), tR=7.79 min, m/z=321.3.

1. additionAdd over 30 min, at room temperature
2. temperatureHeat the solution
3. temperatureto reflux for 5 h
4. customcarefully quench
5. customthe reaction with water and aqueous sodium hydroxide solution
6. customSeparate the phases
7. extractionre-extract the aqueous phase with EtOAc
8. dry with materialDry the combined organic phases over MgSO4
9. customremove the solvent under vacuum
10. customPurify the crude product by column chromatography (CH2Cl2/MeOH/NH4OH 9:2:0.25)