3-Bromoanisole → 2-Dimethylaminomethyl-3-(3-methoxy-phenyl)-bicyclo[3.2.1]octan-3-ol

Temperature

-78 °C

Add dropwise a solution of t-BuLi (19.2 mL, 25.0 mmol) in hexane via syringe to a solution of 1-bromo-3-methoxy-benzene (3.74 g, 20.0 mmol) in THF (60 mL) at −78° C. under N2. After being stirred at −78° C. for 1 hour, add dropwise a solution of 2-dimethylaminomethyl-bicyclo[3.2.1]octan-3-one (1.81 g, 10.0 mmol) in THF (10 mL) to the reaction mixture and stir the resultant mixture at −78° C. for additional 1 hour. Quench the reaction with saturated aqueous NH4Cl solution (20 mL). Extract the aqueous mixture with EtOAc (50 mL×3). The combined organic layers are washed with brine (15 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Purify the residue by silica gel chromatography (CH2Cl2:MeOH=30:1) to afford 2-dimethylaminomethyl-3-(3-methoxy-phenyl)-bicyclo[3.2.1]octan-3-ol as white solid (1.49 g, yield: 51%). MS (m/z): 290 (M+1).

1. customQuench
2. customthe reaction with saturated aqueous NH4Cl solution (20 mL)
3. extractionExtract the aqueous mixture with EtOAc (50 mL×3)
4. washThe combined organic layers are washed with brine (15 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under vacuum
8. customPurify the residue by silica gel chromatography (CH2Cl2:MeOH=30:1)

ORD record

ord-9a71673233814d2e8ea0c383cd95dc79

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802728B2