Methyl iodide → 1-Cyclohexyl-4-methoxymethyl-pyrrolidin-2-one

HRID 2235181Notes

Reaction equation

HRID 2235181 reaction equation
[CH:1]1([N:7]2[CH2:11][CH:10]([CH2:12][OH:13])[CH2:9][C:8]2=[O:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].I[CH3:18]>ClCCl>[CH:1]1([N:7]2[CH2:11][CH:10]([CH2:12][O:13][CH3:18])[CH2:9][C:8]2=[O:14])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 242755161-Cyclohexyl-4-(hydroxymethyl)pyrrolidin-2-one

Product 1

HCID 592995261-Cyclohexyl-4-methoxymethyl-pyrrolidin-2-oneYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 1-cyclohexyl-4-hydroxymethyl-pyrrolidin-2-one (preparation 2) (280 mg, 1.4 mmol) in dichloromethane (30 mL) and cool to 0° C. Add sodium hydride (57 mg, 1.4 mmol) and stir for 20 minutes. Add iodomethane (302 mg, 2.1 mmol) and stir for 24 hours. Quench reaction with water and extract with dichloromethane. Combine extracts, dry over sodium sulfate, filter, and concentrate. Purify by silica gel (1% methanol in ethyl acetate) to give 210 mg (70%) of the title compound. NMR (CDCl3) δ 3.90 (m, 1H), 3.40 (m, 1H), 3.31 (m, 4H), 3.25 (m, 1H), 3.11 (m, 1H), 2.50 (m, 2H), 2.12 (m, 1H), 1.75 (m, 2H), 1.65 (m, 3H), 1.33 (m, 4H), 1.05 (m, 1H).

Workup

  1. customQuench
  2. customreaction with water
  3. extractionextract with dichloromethane
  4. dry with materialCombine extracts, dry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by silica gel (1% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-a48602a237f14827b26abbae7ba348fd
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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