Acetonitrile → 2-(4-Trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazole-5-carboxylic acid ethyl ester

HRID 1172669Notes

Reaction equation

HRID 1172669 reaction equation
Cl.[F:2][C:3]([F:11])([F:10])[CH:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.C(#N)C.[CH2:15]([O:17][C:18]([C:20]1[S:24][C:23]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)=[N:22][C:21]=1[CH2:35]Br)=[O:19])[CH3:16].C(=O)([O-])[O-].[K+].[K+]>O>[CH2:15]([O:17][C:18]([C:20]1[S:24][C:23]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:33])([F:34])[F:32])=[CH:27][CH:26]=2)=[N:22][C:21]=1[CH2:35][N:7]1[CH2:8][CH2:9][CH:4]([C:3]([F:11])([F:10])[F:2])[CH2:5][CH2:6]1)=[O:19])[CH3:16]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 11430Potassium CarbonateHCID 162181604-(Trifluoromethyl)piperidine hydrochlorideHCID 179517684-Bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic Acid Ethyl Ester

Product 1

HCID 595563562-(4-Trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazole-5-carboxylic acid ethyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 107.7 g of 4-trifluoromethyl piperidine hydrochloride in 450 mL of water were added 2.7 L of acetonitrile, 224 g of 4-bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic acid ethyl ester and 157 g of potassium carbonate. The resulting mixture was heated to 40° C. for 2 h, allowed to cool to room temperature then concentrated under reduced pressure. The residue was taken into 2 L of dichloromethane then washed twice with 500 mL of water. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (gradient of dichloromethane/ethanol from 100/0 to 90/10) followed by washing of the collected solid with diisopropyl ether to give 212 g of 2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazole-5-carboxylic acid ethyl ester as a white solid.

Workup

  1. temperatureto cool to room temperature
  2. concentrationthen concentrated under reduced pressure
  3. washthen washed twice with 500 mL of water
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by column chromatography on silica gel (gradient of dichloromethane/ethanol from 100/0 to 90/10)
  8. washby washing of the collected solid with diisopropyl ether

Sources & evidence

ORD record
ord-f9d84cd2734e4e4ab2c8ee2deba8ddb7
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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