Methyl iodide → tert-Butyl(3S)-3-{[tert-butyl(dimethyl)silyloxy]methyl}-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate

HRID 446116Notes

Reaction equation

HRID 446116 reaction equation
[Si:1]([O:8][CH2:9][C@:10]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:14][C:13](=[O:15])[N:12]([C@@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH3:17])[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].IC.[CH3:33][Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl-].[NH4+]>O1CCCC1>[Si:1]([O:8][CH2:9][C@:10]1([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH:14]([CH3:33])[C:13](=[O:15])[N:12]([C@@H:16]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH3:17])[CH2:11]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 57758663tert-butyl(3S)-3-{[tert-butyl(dimethyl)silyloxy]methyl}-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate

Product 1

HCID 57758739tert-Butyl(3S)-3-{[tert-butyl(dimethyl)silyloxy]methyl}-4-methyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylateYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl (3S)-3-{[tert-butyl (dimethyl) silyloxy]methyl}-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (8.65 g, 19.9 mmol) and iodomethane (1.37 mL, 21.9 mmol) in tetrahydrofuran (173 mL), lithium bistrimethylsilyl amide (21.9 mL, 21.9 mmol, 1M solution in tetrahydrofuran) was added in an ice bath, and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture, saturated aqueous solution of ammonium chloride (300 mL) was added, and the mixture was extracted with ethyl acetate (300 mL×2). The organic layer was washed with saturated aqueous solution of sodium chloride (200 mL), and dried with anhydrous sodium sulfate. After the filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (elusion by hexane:ethyl acetate, 7:1→1:1) to obtain 3.72 g (42%) of the title compound (single component) as a colorless oily substance.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (300 mL×2)
  2. washThe organic layer was washed with saturated aqueous solution of sodium chloride (200 mL)
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter the filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (elusion by hexane:ethyl acetate, 7:1→1:1)

Sources & evidence

ORD record
ord-2f3eb253d6c045ada76e01b86ca735db
Source dataset
uspto-grants-2013_07
Patent number
US08476429B2

Reaction notes

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