(3-Bromo-4-fluorophenoxy)(tert-butyl)dimethylsilane → 2-Dimethylaminomethyl-3-(2-fluoro-5-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol

Participants

Reaction Conditions

Reaction Steps

Cool a solution of (3-bromo-4-fluoro-phenoxy)-tert-butyl-dimethyl-silane (5.81 g, 19.03 mmol) in THF (100 mL) to −78° C. under N2. Then add dropwise a solution of t-BuLi (14.6 mL, 19.03 mmol) in hexane via syringe to the reaction solution. After being stirred at −78° C. for 1 hour, add dropwise a solution of 2-dimethylaminomethyl-bicyclo[3.2.1]octan-3-one (2.87 g, 15.86 mmol) in THF (1.5 mL) to the reaction mixture and stir the mixture at −78° C. for additional 1 hour. Quench the reaction with 60 mL of diluted HCl (2N), and stir at ambient temperature for 2 hours. Basify the resultant mixture with K2CO3 to pH=9, and extract with EtOAc (100 mL×3). The combined organic layers are washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. Purify the residue by silica gel chromatography (CH2Cl2 to CH2Cl2:MeOH=10:1) to afford 2-dimethylaminomethyl-3-(2-fluoro-5-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol as white solid (2.38 g, yield: 51.2%). MS (m/z): 294 (M+1).

Provenance & Evidence