Tetrahydrofuran → HCID 66882284, compound

(4,4-Dimethyl-1,1-dioxido-1,2,5-thiadiazolidin-2-yl)triphenylphosphonium (172 mg, 0.420 mmol) was added to a solution of 3-endo-hydroxy-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (95 mg, 0.42 mmol), and 4′-trifluoromethylbiphenyl-3-ol (50 mg, 0.21 mmol) in THF (2 mL). The reaction mixture was stirred for 18 hat ambient temperature. Volatiles were removed under reduced pressure. The resultant material was dissolved in DCM (1 mL) and TFA (1 mL) was added. The reaction mixture was stirred at ambient temperature for 4 h. Volatiles were removed under reduced pressure, the crude product dissolved in methanol (2 mL) and the solution loaded onto a SCX cartridge (5 g). The cartridge was eluted with methanol (3×10 mL) to remove triphenylphosphine oxide. Elution with ammonia in methanol (2M, 10 mL) followed by evaporation in vacuo afforded crude 3-(4′-trifluoromethylbiphenyl-3-yloxy)-8-azabicyclo[3.2.1]octane as an oil. The crude material was then purified by preparative LCMS to afford 3-exo-(4′-trifluoromethylbiphenyl-3-yloxy)-8-azabicyclo[3.2.1]octane as the trifluoroacetic acid salt (36.9 mg, 0.080 mmol, 38%) M.S. (ESI) (m/z): 348 [M+H]+.

1. customVolatiles were removed under reduced pressure
2. dissolutionThe resultant material was dissolved in DCM (1 mL)
3. additionTFA (1 mL) was added
4. stirringThe reaction mixture was stirred at ambient temperature for 4 h
5. customVolatiles were removed under reduced pressure
6. dissolutionthe crude product dissolved in methanol (2 mL)
7. washThe cartridge was eluted with methanol (3×10 mL)
8. customto remove triphenylphosphine oxide
9. washElution with ammonia in methanol (2M, 10 mL)
10. customfollowed by evaporation in vacuo

ORD record

ord-e68e57912c4e49bdb1cbee9815ba9aa1

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07605170B2