Sodium hydride → 1-({4-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)-3,3-diphenylpyrrolidin-2-one

HRID 1667199

Reaction equation

HRID 1667199 reaction equation
[C:1]1([C:7]2([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:22][C:23]1[S:27][C:26]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[N:25][C:24]=1[CH3:38]>CN(C)C=O>[CH3:38][C:24]1[N:25]=[C:26]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:32][CH:33]=2)[S:27][C:23]=1[CH2:22][N:9]1[CH2:10][CH2:11][C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:8]1=[O:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2382533,3-Diphenyl-2-pyrrolidinoneHCID 27946295-(Bromomethyl)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole

Product 1

HCID 673577121-({4-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)-3,3-diphenylpyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3,3-diphenylpyrrolidin-2-one (Example 1A) (0.062 g, 0.262 mmol) in N,N-dimethylformamide (2 mL) was added 60% sodium hydride dispersion in oil (0.013 g, 0.314 mmol). The mixture was stirred at room temperature for 1 hour. Then a solution of 5-(bromomethyl)-4-methyl-2-(4-(trifluoromethyl)phenyl)thiazole (CAS 439134-78-8) (0.088 g, 0.262 mmol) in N,N-dimethylformamide (1 mL) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated and the residue was partitioned between H2O and dichloromethane. The organic layer was separated, dried over MgSO4 and concentrated. The obtained residue was purified by silica gel chromatography eluting with 2-5% methanol/dichloromethane to yield the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.95-8.00 (m, 2H), 7.65-7.70 (m, 2H), 7.17-7.37 (m, 10H), 4.72 (s, 2H), 3.35 (t, J=6.4 Hz, 2H), 2.76 (t, J=6.3 Hz, 2H), 2.47 (s, 3H); MS (ESI+) m/z 493 (M+H)+.

Workup

  1. stirringthe mixture was stirred at room temperature overnight
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was partitioned between H2O and dichloromethane
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customThe obtained residue was purified by silica gel chromatography
  8. washeluting with 2-5% methanol/dichloromethane

Sources & evidence

ORD record
ord-2d1f68eb38ba429f8a4192d98f758751
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Linked notes

Loading…