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

HRID 15077

Reaction equation

HRID 15077 reaction equation
[H-].[Na+].CN(C=O)C.[OH:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]1.C1(C)C=CC(S(O[CH2:31][CH2:32][F:33])(=O)=O)=CC=1>C(OCC)(=O)C>[F:33][CH2:32][CH2:31][O:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2560192-Fluoroethyl p-ToluenesulfonateHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 86614896tert-butyl (3R)-3-(2-fluoroethoxy)pyrrolidine-1-carboxylateYield 41%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

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%).

Workup

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

Sources & evidence

ORD record
ord-85ad0e45c6a6422c9234ea193065d75c
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Linked notes

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