1-(Bromomethyl)-4-(trifluoromethyl)benzene → 3-[4-(Trifluoromethyl)benzyl]pyrrolidin-2-one

HRID 2235300Notes

Reaction equation

HRID 2235300 reaction equation
C([Si](C)(C)O[C@@H]1CC[C@H]([N:13]2[CH2:17][CH2:16][CH2:15][C:14]2=[O:18])CC1)(C)(C)C.[F:21][C:22]([F:32])([F:31])[C:23]1[CH:30]=[CH:29][C:26]([CH2:27]Br)=[CH:25][CH:24]=1.[Li+].CC([N-]C(C)C)C>>[F:21][C:22]([F:31])([F:32])[C:23]1[CH:30]=[CH:29][C:26]([CH2:27][CH:15]2[CH2:16][CH2:17][NH:13][C:14]2=[O:18])=[CH:25][CH:24]=1

Participants

4

Reactant 3

HCID 1230621-(Bromomethyl)-4-(trifluoromethyl)benzeneHCID 2724682Lithium diisopropylamideHCID 178455336HCID 178455336, compound

Product 1

HCID 713002843-[4-(Trifluoromethyl)benzyl]pyrrolidin-2-oneYield 39%

Procedure

Using the procedure to synthesize Example 202 and using cis-1-[4-(tert-butyl-dimethyl-silanyloxy)-cyclohexyl]-pyrrolidin-2-one (Preparation 17), 4-trifluoromethyl benzylbromide and 1.5 equivalents of LDA affords an oil. Chromatography (silica, 4:1 hexanes/EtoAc) yields 4-[4-tert-butyl dimethyl-silanyloxy)-cyclohexyl]-3-(4-trifluoromethyl-benzyl)-pyrrolidin-2-one in 39% yield. The silylether is dissolved in THF, treated with 5.0 equivalents of TBAF and allowed to stir at room temperature overnight. Quench reaction with water, dilute with methylene chloride, separate, dry over sodium sulfate, filter and evaporate. Chromatography (silica, 4:6 hexanes/EtoAc) provides the titled compound in 21% yield: Mass spectrum (API-ES positive) m/z=342.3 (M+H).

Workup

  1. customto synthesize Example 202
  2. customaffords an oil

Sources & evidence

ORD record
ord-abcfaccec3c94a8f81f5508888172a81
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

Loading…