Dimethylformamide → Tert-butyl 4-(2-{[4-bromo-2-(trifluoromethyl)phenyl]sulfanyl}ethyl)piperidine-1-carboxylate

HRID 522258Notes

Reaction equation

HRID 522258 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].[Br:33][C:34]1[CH:39]=[CH:38][C:37]([SH:40])=[C:36]([C:41]([F:44])([F:43])[F:42])[CH:35]=1.CN(C=O)C>CCOC(C)=O.O>[Br:33][C:34]1[CH:39]=[CH:38][C:37]([S:40][CH2:12][CH2:13][CH:14]2[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:18][CH2:19]2)=[C:36]([C:41]([F:44])([F:42])[F:43])[CH:35]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 21936070N-Boc-4-[2-(4-Toluenesulfonyloxy)ethyl]piperidineHCID 509979974-Bromo-2-(trifluoromethyl)benzenethiol

Product 1

HCID 117899583Tert-butyl 4-(2-{[4-bromo-2-(trifluoromethyl)phenyl]sulfanyl}ethyl)piperidine-1-carboxylateYield 87.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyl 4-(2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)piperidine-1-carboxylate (2.65 g) and potassium carbonate (2.0 g) were added to a mixture of 4-bromo-2-(trifluoromethyl)benzenethiol (1.8 g) and DMF (20 mL) at room temperature, and the mixture was stirred at the same temperature overnight. The reaction mixture was further stirred at 80° C. for 3 hours. After the reaction mixture was cooled to room temperature, water (50 mL) and EtOAc (30 mL) were added thereto, then extraction thereof was performed using EtOAc, and the extract was washed with saturated brine. The organic layer was dried over MgSO4 and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Hex:EtOAc=100:0 to 80:20), whereby tert-butyl 4-(2-{[4-bromo-2-(trifluoromethyl)phenyl]sulfanyl}ethyl)piperidine-1-carboxylate (2.83 g) was obtained as a colorless oil.

Workup

  1. stirringThe reaction mixture was further stirred at 80° C. for 3 hours
  2. extractionextraction
  3. washthe extract was washed with saturated brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (Hex:EtOAc=100:0 to 80:20)

Sources & evidence

ORD record
ord-fd19702f007a4b3ba0747c4323cc9b6c
Source dataset
uspto-grants-2016_05
Patent number
US09328118B2

Reaction notes

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