Reaction #43355

Reaction equation

2-fluoroethyl p-toluenesulfonate

Sodium hydride

DMF

tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

→

title compound

Yield 41.0%

tert-butyl (3R)-3-(2-fluoroethoxy)pyrrolidine-1-carboxylate

Yield 41.0%

Solvents

Ethyl acetate

Conditions

Workup

1. 1
   workup.STIRRINGstirring at the same temperature
2. 2
   Washthen was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine
3. 3
   Dryingdried over anhydrous magnesium sulfate
4. 4
   ConcentrationConcentrating the solvent under reduced pressure
5. 5
   Otherthe residue was purified on silica gel column chromatography (KP-Sil Sil FLASH 25+M, ethyl acetate:hexane=1:10→2:8)

Procedure

Sodium hydride (55% oiliness, 140 mg, 3.2 mmols) was added to DMF (5 mL) solution of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (501.2 mg, 2.7 mmols) and stirred at room temperature for 30 minutes, followed by addition of 2-fluoroethyl p-toluenesulfonate (1.17 g, 5.4 mmols) and further 24 hours' stirring at the same temperature. Ethyl acetate was added to the reaction liquid which then was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, and dried over anhydrous magnesium sulfate. Concentrating the solvent under reduced pressure, the residue was purified on silica gel column chromatography (KP-Sil Sil FLASH 25+M, ethyl acetate:hexane=1:10→2:8) to provide the title compound (253 mg, 41%).

Source