Tert-butyl 3-oxopyrrolidine-1-carboxylate → Tert-butyl 3-hydroxy-3-(trifluoromethyl)pyrrolidine-1-carboxylate

Temperature

0 °C

tert-Butyl 3-oxopyrrolidine-1-carboxylate (926 mg, 5.0 mmol) was dissolved in THF (10 mL) and the solution was cooled to 0° C., trimethyl(trifluoromethyl)silane (0.872 mL) and tetrabutylammonium fluoride (TBAF) (176 mg, 0.557 mmol) were added. The ice-bath was removed and the reaction mixture was stirred at room temperature overnight. Saturated aqueous NH4Cl solution (8 mL) was added and stirring was continued. After 15 min TBAF (2.36 g TBAF in 7.5 mL THF) was added and the reaction mixture was stirred at room temperature for 1 h. The reaction mixture was extracted with ethyl acetate, washed with H2O, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash chromatography (0-40% ethyl acetate in petroleum spirit) to give the subtitled compound (800 mg).

1. customThe ice-bath was removed
2. additionSaturated aqueous NH4Cl solution (8 mL) was added
3. stirringstirring
4. additionAfter 15 min TBAF (2.36 g TBAF in 7.5 mL THF) was added
5. stirringthe reaction mixture was stirred at room temperature for 1 h
6. extractionThe reaction mixture was extracted with ethyl acetate
7. washwashed with H2O
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by silica gel flash chromatography (0-40% ethyl acetate in petroleum spirit)

ORD record

ord-a6b254a7963647e2a0a6eee234177e7a

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07449475B2