Sodium hydride → (S)-1-Benzyl-2-(2,2,2-trifluoro-ethoxymethyl)-pyrrolidine

To a suspension of sodium hydride (60% in mineral oil, 0.314 g, 7.84 mmol) in THF (20 mL) was added (S)-(1-benzyl-pyrrolidin-2-yl)-methanol (1.0 g, 5.23 mmol) and the reaction mixture was stirred at room temperature for 20 min. Then, 2,2,2-trifluoroethyl methanesulfonate (1.4 g, 7.84 mmol) was added and stirring was continued at room temperature over night. The reaction mixture was quenched with H2O (10 mL) and extracted with EtOAc (2×50 mL). Combined organics were dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH(1% NH4OH)-DCM gradient to give the title compound (0.706 g, 37%) as a light yellow liquid. MS: 274.3 (M+H+).

1. stirringstirring
2. waitwas continued at room temperature over night
3. customThe reaction mixture was quenched with H2O (10 mL)
4. extractionextracted with EtOAc (2×50 mL)
5. dry with materialCombined organics were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel flash chromatography
9. washeluting with a 0 to 5% MeOH(1% NH4OH)-DCM gradient

ORD record

ord-1045b6b2241b49d197d088c8ceac86f1

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260408B2