Methyl iodide → (5S)-5-[(tert-butyldimethylsilyloxy)methyl]-1-methylpyrrolidin-2-one

HRID 497070Notes

Reaction equation

HRID 497070 reaction equation
[Si:1]([O:8][CH2:9][C@H:10]1[NH:14][C:13](=[O:15])[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH3:18]I.[NH4+].[Cl-]>C1COCC1>[Si:1]([O:8][CH2:9][C@H:10]1[N:14]([CH3:18])[C:13](=[O:15])[CH2:12][CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 10263224(S)-5-(((tert-Butyldimethylsilyl)oxy)methyl)pyrrolidin-2-one

Product 1

HCID 18639170(5S)-5-[(tert-butyldimethylsilyloxy)methyl]-1-methylpyrrolidin-2-oneYield 97.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A THF (10 ml) solution of the (5S)-5-[(tert-butyldimethylsilyloxy)methyl]pyrrolidin-2-one (3.71 g, 16.2 mmols) was added dropwise to a THF (70 ml) suspension of NaH (60% oil disp. 778 mg, 19.4 mmols), with the system being cooled with ice, whereafter the mixture was stirred for 30 minutes at room temperature. To the mixture, MeI (5.0 ml, 81 mmols) was added during cooling with ice, and the mixture was stirred for 15 hours at room temperature. During cooling with ice, a saturated aqueous solution (50 ml) of NH4Cl was added, and the solvent was distilled off under reduced pressure. The residue was diluted with water, whereafter the dilution was extracted with AcOEt (50 ml×3), and the organic layer was dried over MgSO4. The solvent was distilled off under reduced pressure, and then the residue was subjected to silica gel column chromatography (SiO2 150 g, MeOH—CHCl3 3:97 v/v) to obtain (5S)-5-[(tert-butyldimethylsilyloxy)methyl]-1-methylpyrrolidin-2-one (3.86 g, 97.9%): [α]D29+3.46 (c 1.13, CHCl3). IR νmax (film) cm−1: 1682. 1H-NMR (CDCl3)δ: 3.73 (1H, dd, J=10.2, 3.3 Hz), 3.60 (1H, dd, J=10.2, 4.1 Hz), 3.55 (1H, quint, J=4.1 Hz), 2.85 (3H, s), 2.50-2.37 (1H, m), 2.35−2.23 (1H, m), 2.15-2.01 (1H, m), 1.89-1.77 (1H, m), 0.89 (9H, s), 0.06 (3H, s), 0.05 (3H, s). MS m/z: 228 (M+−15), 186, 98 (100%). HRMS: Calculated for C11H22NO2Si: 228.1420 (M+−15). Found: 228.1441 (M+−15).

Workup

  1. temperaturebeing cooled with ice, whereafter the mixture
  2. temperatureduring cooling with ice
  3. stirringthe mixture was stirred for 15 hours at room temperature
  4. temperatureDuring cooling with ice
  5. distillationthe solvent was distilled off under reduced pressure
  6. additionThe residue was diluted with water, whereafter the dilution
  7. extractionwas extracted with AcOEt (50 ml×3)
  8. dry with materialthe organic layer was dried over MgSO4
  9. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-7b84de00ba5d4a0b918eb0edca452d50
Source dataset
uspto-grants-2005_09
Patent number
US06949553B2

Reaction notes

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