Tetrabutylammonium Fluoride → HCID 60152194, compound

Temperature

-78 °C

Add a solution of t-BuLi (19.4 mL, 25.2 mmol) via syringe to a solution of (3-bromo-5-fluoro-phenoxy)-tert-butyl-dimethyl-silane (6.99 g, 22.9 mmol) in THF (100 mL) at −78° C. under N2. After being stirred at −78° C. for 1 hour, add dropwise a solution of 3-dimethylaminomethyl-bicyclo[4.1.0]heptan-2-one (2.55 g, 15.3 mmol) to the reaction mixture and stir the reaction mixture at −78° C. for additional 2 hours. Quench the reaction with saturated NH4Cl solution (30 mL). Extract the resultant aqueous mixture with EtOAc (100 mL×3). The combined organic layers are washed with brine (30 mL), dried over Na2SO4, filtered, and concentrated under vacuum. Treat the residue with TBAF (6.00 g, 22.9 mmol) in CH2Cl2 (80 mL) at ambient temperature for 4 hours. Concentrate the mixture, and purify the residue by preparative HPLC to give 3-dimethylaminomethyl-2-(3-fluoro-5-hydroxy-phenyl)-bicyclo[4.1.0]heptan-2-ol as white solid (592 mg, yield: 13.9%). MS (m/z): 280 (M+1).

1. stirringstir the reaction mixture at −78° C. for additional 2 hours
2. customQuench
3. customthe reaction with saturated NH4Cl solution (30 mL)
4. extractionExtract the resultant aqueous mixture with EtOAc (100 mL×3)
5. washThe combined organic layers are washed with brine (30 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated under vacuum
9. concentrationConcentrate the mixture
10. custompurify the residue by preparative HPLC

ORD record

ord-853b84315c234c7299aa0b511745e788

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08802728B2