Toluene → tert-Butyl(3R)-3-fluoromethyl-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate

HRID 229554Notes

Reaction equation

HRID 229554 reaction equation
O[CH2:2][C@:3]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:7]([CH3:8])[C:6](=[O:9])[N:5]([C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:11])[CH2:4]1.C1(C)C=CC=CC=1.C(N(S(F)(F)[F:38])CC)C.C(=O)([O-])O.[Na+]>ClCCl>[F:38][CH2:2][C@:3]1([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH:7]([CH3:8])[C:6](=[O:9])[N:5]([C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:11])[CH2:4]1

Participants

6

Reactant 4

HCID 1140TolueneHCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 57758675tert-Butyl(3S)-3-hydroxymethyl-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate

Product 1

HCID 57758660tert-Butyl(3R)-3-fluoromethyl-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylateYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

Tert-butyl(3S)-3-hydroxymethyl-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (1.70 g, 5.10 mmol) was dissolved in dichloromethane (20 mL). To this solution, toluene (20 mL) was added, and diethylaminosulfur trifluoride (1.68 mL, 12.8 mmol) was added dropwise in an ice bath. After stirring at 60° C. for 8 hours, saturated aqueous solution of sodium hydrogencarbonate (50 mL) was added to the reaction mixture, and the mixture was extracted by ethyl acetate (100 mL×2). The organic layer was washed with saturated aqueous solution of sodium chloride (100 mL), and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The concentrate was then purified by silica gel column chromatography (solution by hexane:ethyl acetate, 9:1→2:3) to obtain 0.910 mg (53%) of the title compound as a pale yellow oily substance.

Workup

  1. extractionthe mixture was extracted by ethyl acetate (100 mL×2)
  2. washThe organic layer was washed with saturated aqueous solution of sodium chloride (100 mL)
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe concentrate was then purified by silica gel column chromatography (solution by hexane:ethyl acetate, 9:1→2:3)

Sources & evidence

ORD record
ord-ee49e7fc24d0432a870f1c58894fa0b0
Source dataset
uspto-grants-2009_07
Patent number
US07563805B2

Reaction notes

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