Sodium hydride → (R)-1-(5-Benzyloxypentyl)-4-butylpyrrolidin-2-one

HRID 273187Notes

Reaction equation

HRID 273187 reaction equation
[CH2:1]([C@H:5]1[CH2:9][NH:8][C:7](=[O:10])[CH2:6]1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[CH2:13]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>CN(C)C=O.C(OCC)(=O)C>[CH2:13]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][N:8]1[CH2:9][C@H:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:6][C:7]1=[O:10])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 14221121Benzyl 5-Bromoamyl EtherHCID 55287323(R)-4-butylpyrrolidin-2-one

Product 1

HCID 69310462(R)-1-(5-Benzyloxypentyl)-4-butylpyrrolidin-2-oneYield 95%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-4-butylpyrrolidin-2-one (0.42 g, 2.9 mmol) in dry dimethylformamide (10 mL) under argon was slowly added sodium hydride (60% in mineral oil, 0.14 g, 3.5 mmol) at 0° C. After stirring at 0° C. for 30 minutes, 5-benzyloxypentyl bromide (0.9 g, 3.5 mmol) was added dropwise. The resulting mixture was stirred at room temperature overnight and then diluted with ethyl acetate (50 mL). The organic solution was washed with water (4×30 mL) and brine (30 mL), dried (Na2SO4) and concentrated. The residue was purified by flash column chromatography (silica gel, 1:1 EtOAc/hexanes) to afford 0.73 g (95%) of (R)-1-(5-benzyloxypentyl)-4-butylpyrrolidin-2-one as a colorless oil: 1H NMR (CDCl3) δ 7.33 (m, 5 H), 4.51 (s, 2 H), 3.45 (m, 3 H), 3.27 (t, 2 H), 2.99 (dd, 1 H), 2.52 (dd, 1 H), 2.32 (m, 1 H), 2.06 (m, 1 H), 1.24-1.71 (m, 12 H), 0.93 (t, 3 H). MS(ES) m/e 318 [M+H]+.

Workup

  1. customat 0° C
  2. stirringThe resulting mixture was stirred at room temperature overnight
  3. washThe organic solution was washed with water (4×30 mL) and brine (30 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography (silica gel, 1:1 EtOAc/hexanes)

Sources & evidence

ORD record
ord-3b31c9d39aee423b877ab9bdbfc67daf
Source dataset
uspto-grants-2008_11
Patent number
US07456211B2

Reaction notes

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