Sodium Carbonate → Ethyl 4-[4-(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate

HRID 1766112Notes

Reaction equation

HRID 1766112 reaction equation
Br[CH2:2][C:3]1[N:4]=[C:5]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=2)[S:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C(=O)([O-])[O-].[Na+].[Na+].[F:29][C:30]([F:41])([F:40])[C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1>COCCOCCOC.O.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:29][C:30]([F:41])([F:40])[C:31]1[CH:36]=[CH:35][C:34]([CH2:2][C:3]2[N:4]=[C:5]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)[S:6][C:7]=2[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:33][CH:32]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 179517684-Bromomethyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carboxylic Acid Ethyl Ester

Product 1

HCID 17951848Ethyl 4-[4-(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylateYield 35%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8150DiglymeSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of ethyl 4-(bromomethyl)-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate (0.25 g, 0.63 mmol) in 4 ml of 2-methoxyethyl ether was added tetrakis(triphenylphosphine)palladium(0), (0.02 g, 0.019 mmol) and then sodium carbonate (0.13 g, 1.2 mmol) in 0.5 ml water. After brief stirring, 4-(trifluoromethyl)phenyl boronic acid (0.13 g, 0.7 mmol) in 1 ml ethanol was added. After heating at 110° C. for 15 hours, the reaction was complete by HPLC and was treated with water (5 ml) and extracted with tert-butyl methyl ether (2×30 ml). The organic layers were dried with magnesium sulfate and immediately loaded onto silica to give a crude residue which was purified on a Biotage FlashElute with a 40M silica cartridge, eluting with 10% ethyl acetate in hexanes to yield ethyl 4-[4-(trifluoromethyl)benzyl]-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole-5-carboxylate as a white solid (0.09 g, 35%).

Workup

  1. extractionextracted with tert-butyl methyl ether (2×30 ml)
  2. dry with materialThe organic layers were dried with magnesium sulfate
  3. customto give a crude residue which
  4. customwas purified on a Biotage FlashElute with a 40M silica cartridge
  5. washeluting with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c6eb4816868e44cd92d5f66417296a76
Source dataset
uspto-grants-2007_06
Patent number
US07229998B2

Reaction notes

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