Imidazole → 5-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one

HRID 458963Notes

Reaction equation

HRID 458963 reaction equation
[OH:1][CH:2]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:3][CH2:4][CH:5]1[NH:9][C:8](=[O:10])[CH2:7][CH2:6]1.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].N1C=CN=C1>CN(C=O)C.CN(C1C=CN=CC=1)C>[C:21]([Si:18]([CH3:20])([CH3:19])[O:1][CH:2]([CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[CH2:3][CH2:4][CH:5]1[NH:9][C:8](=[O:10])[CH2:7][CH2:6]1)([CH3:24])([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 129700845-(3-Hydroxy4-phenyl-butyl)-pyrrolidin-2-one

Product 1

HCID 129700855-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-oneYield 92.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(3-hydroxy-4-phenyl-butyl)-pyrrolidin-2-one (4.3 g, 18.43 mmol) in DMF (86 mL) was added tert-butyldimethylsilyl chloride (3.06 g, 20.3 mmol) followed by imidazole (2.5 g, 37 mmol) and DMAP (225 mg). The reaction mixture was stirred for 24 h and was quenched with saturated aqueous ammonium chloride. The aqueous solution was washed with EtOAc (3×) and the combined organic extracts were dried (MgSO4), filtered and concentrated. The residue was purified by medium pressure chromatography eluting with a solvent gradient (CH2Cl2 to 1% MeOH in CH2Cl2 to 2% MeOH in CH2Cl2) to yield 5.94 g of 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one. 1H NMR (CDCl3) δ7.26–7.10 (m, 5H), 5.68 (m, 1H), 3.83 (m, 1H), 3.54 (m, 1H), 2.69 (m, 2H), 2.30–2.16 (m, 3H), 1.66–1.35 (m, 5H), 0.82 (s, 9H), −0.06 (d, 3H), −0.2 (d, 3H).

Workup

  1. customwas quenched with saturated aqueous ammonium chloride
  2. washThe aqueous solution was washed with EtOAc (3×)
  3. dry with materialthe combined organic extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by medium pressure chromatography
  7. washeluting with a solvent gradient (CH2Cl2 to 1% MeOH in CH2Cl2 to 2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-935e4395c54343669d80ccc3dbb3336a
Source dataset
uspto-grants-2007_03
Patent number
US07192979B2

Reaction notes

Loading…