Sodium hydride → (S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-chlorobenzyl)pyrrolidin-2-one

HRID 1507280Notes

Reaction equation

HRID 1507280 reaction equation
[H-].[Na+].[Si:3]([O:10][C@H:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4].Br[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1>C1COCC1>[Si:3]([O:10][C@H:11]1[CH2:15][CH2:14][N:13]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[C:12]1=[O:16])([C:6]([CH3:9])([CH3:8])[CH3:7])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 10584804(S)-3-((tert-Butyldimethylsilyl)oxy)pyrrolidin-2-one

Product 1

HCID 123669991(S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-chlorobenzyl)pyrrolidin-2-oneYield 47.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 60% dispersion of sodium hydride in mineral oil (0.608 g, 13.9 mmol) was added to a stirred solution of (S)-3-((tert-butyldimethylsilyl)oxy)pyrrolidin-2-one (2.0 g, 9.29 mmol, from example 114, step A) in THF (7 mL) at 0° C. After 15 min, a solution of 1-(bromomethyl)-4-chlorobenzene (1.72 g, 8.37 mmol) in THF (7 mL) was added to the reaction mixture. The resulting mixture was stirred at RT for 6 h. The reaction was quenched with pellets of ice. The resulting mixture was extracted with EtOAc. The combined organic layers were washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The crude reaction mixture was purified using silica gel column chromatography (0-15% EtOAc/hexanes) to afford (S)-3-((tert-butyldimethylsilyl)oxy)-1-(4-chlorobenzyl)pyrrolidin-2-one (1.34 g, 42% yield): LCMS (M+H)+ 340.2; 1H NMR (500 MHz, chloroform-d) δ 1H NMR (500 MHz, chloroform-d) δ 7.36-7.29 (m, J=8.4 Hz, 2H), 7.23-7.16 (m, J=8.4 Hz, 2H), 4.51-4.33 (m, 3H), 3.31-3.22 (m, 1H), 3.11 (dt, J=9.7, 7.4 Hz, 1H), 2.37-2.25 (m, 1H), 1.97-1.84 (m, 1H), 0.95 (s, 9H), 0.21 (s, 3H), 0.18 (s, 3H).

Workup

  1. customThe reaction was quenched with pellets of ice
  2. extractionThe resulting mixture was extracted with EtOAc
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude reaction mixture
  8. customwas purified

Sources & evidence

ORD record
ord-36d922deaf4a4654a750261bacff339c
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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