Sodium t-butoxide → N-{4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-2-methylbenzyl}acetamide

HRID 1930514Notes

Reaction equation

HRID 1930514 reaction equation
CC(C)([O-])C.[Na+].[Cl:7][C:8]1[CH:9]=[C:10]([C:15]2([C:20]([F:23])([F:22])[F:21])[CH2:19][CH2:18][NH:17][CH2:16]2)[CH:11]=[C:12]([Cl:14])[CH:13]=1.Br[C:25]1[CH:35]=[CH:34][C:28]([CH2:29][NH:30][C:31](=[O:33])[CH3:32])=[C:27]([CH3:36])[CH:26]=1>C1(C)C=CC=CC=1.C(OC)(C)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Cl:14][C:12]1[CH:11]=[C:10]([C:15]2([C:20]([F:23])([F:22])[F:21])[CH2:19][CH2:18][N:17]([C:25]3[CH:35]=[CH:34][C:28]([CH2:29][NH:30][C:31](=[O:33])[CH3:32])=[C:27]([CH3:36])[CH:26]=3)[CH2:16]2)[CH:9]=[C:8]([Cl:7])[CH:13]=1

Participants

7

Reactant 3

HCID 23676156Sodium t-butoxideHCID 582188803-(3,5-Dichlorophenyl)-3-(trifluoromethyl)pyrrolidineHCID 66719830N-(4-bromo-2-methylbenzyl)acetamide

Product 1

HCID 66719869N-{4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-2-methylbenzyl}acetamideYield 65.2%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 1140TolueneSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
80 °C

Procedure

Sodium tert-butoxide (0.3 g), Tris(dibenzylidene acetone)dipalladium(0) (chloroform adduct) (0.04 g) and xantphos (0.07 g) was added to the solution of 3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidine (0.59 g) and N-(4-bromo-2-methylbenzyl)acetamide (0.5 g) in toluene under argon atmosphere, and the mixture was heated with stirring at 80° C. for 5 hours. The reaction solution was diluted with t-butylmethylether and then washed with water and brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled away under the reduced pressure, and the residue was then purified by silica gel chromatography to yield N-{4-[3-(3,5-dichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-2-methylbenzyl}acetamide (0.6 g). 1H-NMR (CDCl3) δ: 2.13-2.18 (6H, m), 2.51-2.53 (1H, m), 2.81-2.83 (1H, m), 3.45-3.56 (2H, m), 3.75-3.78 (1H, m), 4.01-4.04 (1H, m), 4.25 (1H, s), 4.57 (1H, s), 6.40-6.44 (2H, m), 6.93-6.96 (1H, m), 7.30-7.38 (3H, m)

Workup

  1. temperaturethe mixture was heated
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled away under the reduced pressure
  5. customthe residue was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-9a1e2c98baeb474f927efec4ca2637e5
Source dataset
uspto-grants-2012_05
Patent number
US08188122B2

Reaction notes

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