Methyl iodide → 4-{3-[2,6-bis(trifluoromethyl)pyridin-4-yl]-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl}-2-bromobenzyl acetate

HRID 2172532Notes

Reaction equation

HRID 2172532 reaction equation
CC([O-])(C)C.[K+].[C:7]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18](=S)[NH:19][CH2:20][Si](C)(C)C)=[CH:14][C:13]=1[Br:26])(=[O:9])[CH3:8].IC.[F:29][C:30]([F:48])([F:47])[C:31]1[CH:36]=[C:35]([C:37]([C:39]([F:42])([F:41])[F:40])=[CH2:38])[CH:34]=[C:33]([C:43]([F:46])([F:45])[F:44])[N:32]=1.[N+](CCCC)(CCCC)(CCCC)CCCC.[F-]>C1COCC1.C(OC)(C)(C)C>[C:7]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH2:38][C:37]([C:35]3[CH:36]=[C:31]([C:30]([F:29])([F:47])[F:48])[N:32]=[C:33]([C:43]([F:46])([F:44])[F:45])[CH:34]=3)([C:39]([F:42])([F:41])[F:40])[CH2:20][N:19]=2)=[CH:14][C:13]=1[Br:26])(=[O:9])[CH3:8]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 2724141Tetrabutylammonium FluorideHCID 23665647Potassium tert-butoxideHCID 580920912-Bromo-4-{[(trimethylsilyl)methyl]carbamothioyl}benzyl acetateHCID 866646212,6-Bis(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)pyridine

Product 1

HCID 866646224-{3-[2,6-bis(trifluoromethyl)pyridin-4-yl]-3-(trifluoromethyl)-3,4-dihydro-2H-pyrrol-5-yl}-2-bromobenzyl acetateYield 37.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

Under argon atmosphere, t-BuOK (0.36 g) was slowly added to 2-bromo-4-{[(trimethylsilyl)methyl]carbamothioyl}benzyl acetate (1.0 g) and iodomethane (0.45 g) in THF at −10° C., and the resultant mixture was stirred for 30 minutes at the same temperature. 2,6-bis(trifluoromethyl)-4-(3,3,3-trifluoroprop-1-en-2-yl)pyridine (1.1 g) was added to the reaction mixture, and then n-Bu4NF in THF (0.25 ml, 1M solution) was slowly added to the mixture at −10° C. under argon atmosphere. After stirring the resultant blend for 30 minutes at the same temperature, the blend was allowed to slowly warm to room temperature. The blend was stirred at room temperature overnight. The blend was diluted with t-BuOMe, and washed with 1N HCl and brine. The organic layer was dried over MgSO4. The solvent was evaporated under reduced pressure and the residue was purified by column chromatography to get the targeted product (0.58 g).

Workup

  1. stirringThe blend was stirred at room temperature overnight
  2. washwashed with 1N HCl and brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-06f6a04c5b814e788dbacaad4f9dde3c
Source dataset
uspto-grants-2015_06
Patent number
US09055749B2

Reaction notes

Loading…