Reaction #45907

Reaction equation

sodium hydride

Methyl iodide

tert-butyl 5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate

citric acid

sodium hydride

→

compound

Yield 36.0%

tert-Butyl(3S)-3-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate

Yield 36.0%

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   workup.STIRRINGby stirring at room temperature for 13 hours
2. 2
   workup.ADDITIONwas added to the reaction liquid
3. 3
   Extractionfollowed by extraction with ethyl acetate
4. 4
   WashThe organic layer was washed with saturated brine
5. 5
   Dryingdried over anhydrous sodium sulfate
6. 6
   Otherthe solvent was evaporated away
7. 7
   OtherThe resulting residue was separated
8. 8
   Otherpurified by silica gel column chromatography (eluent, n-hexane

Procedure

Methyl iodide (21.8 ml, 0.35 mol) was added to an N,N-dimethylformamide (150 ml) solution of tert-butyl 5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (I-341) (20.28 g, 70.1 mmol), then at room temperature, sodium hydride (55%, w/w) (1 g) was added, followed by stirring as such. Afterwards, sodium hydride (1.9 g, 2.7 g, 2.79 g, 1.97 g) was successively added, followed by stirring at room temperature for 13 hours. With cooling with ice, aqueous 10% citric acid solution was added to the reaction liquid, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated away. The resulting residue was separated and purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=3:1, v/v) to obtain the entitled compound (7.65 g, 36%).

Source