Trifluoroacetic acid → 5-(4-Fluoro-phenyl)-2-methyl-thiazole-4-carboxylic Acid Methyl-[2-(2,2,2-trifluoro-ethanoylamino)-ethyl]-amide

HRID 2376692Notes

Reaction equation

HRID 2376692 reaction equation
CC(O[C:6](=[O:18])[N:7]([CH3:17])[CH2:8][CH2:9][NH:10][C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])(C)C.FC(F)(F)C(O)=O.C([O-])([O-])=O.[K+].[K+].[F:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[S:43][C:42]([CH3:44])=[N:41][C:40]=2C(O)=O)=[CH:35][CH:34]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>ClCCl>[CH3:17][N:7]([CH2:8][CH2:9][NH:10][C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])[C:6]([C:40]1[N:41]=[C:42]([CH3:44])[S:43][C:39]=1[C:36]1[CH:35]=[CH:34][C:33]([F:32])=[CH:38][CH:37]=1)=[O:18]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10635722Methyl-[2-(2,2,2-trifluoro-acetylamino)-ethyl]-carbamic acid tert-butyl esterHCID 223241255-(4-Fluorophenyl)-2-methyl-1,3-thiazole-4-carboxylic acid

Product 1

HCID 865997195-(4-Fluoro-phenyl)-2-methyl-thiazole-4-carboxylic Acid Methyl-[2-(2,2,2-trifluoro-ethanoylamino)-ethyl]-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

An ice-cooled solution of methyl-[2-(2,2,2-trifluoro-ethanoylamino)-ethyl]-carbamic acid dimethyl-ethyl ester, D3 (3.61 g, 13.4 mmol) in dichloromethane (80 ml) was treated with trifluoroacetic acid (20 ml). After stirring at room temperature for 5 h the mixture was poured cautiously onto solid K2CO3 (excess)/ice. The product was extracted with dichloromethane (4×) then 10% methanol-dichloromethane (5×). The combined organics were dried (MgSO4) and the solvent removed in vacuo. The resulting yellow gum (380 mg) was added to a stirring solution of 5-(4-fluoro-phenyl)-2-methyl-thiazole-4-carboxylic acid (530 mg, 2.2 mmol), N,N-diisopropylethylamine (1.17 ml, 6.7 mmol) and HATU (851 mg, 2.2 mmol). The reaction mixture was stirred at room temperature, under argon for 16 h, then partitioned between ethyl acetate and water. The organic phase was washed with water (2×), brine, dried (MgSO4) and the solvent removed in vacuo. Chromatography (silica gel, 20–100% ethyl acetate-pentane) afforded the title compound as a colourless gum (443 mg).

Workup

  1. extractionThe product was extracted with dichloromethane (4×)
  2. dry with materialThe combined organics were dried (MgSO4)
  3. customthe solvent removed in vacuo
  4. stirringThe reaction mixture was stirred at room temperature, under argon for 16 h
  5. custompartitioned between ethyl acetate and water
  6. washThe organic phase was washed with water (2×), brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-7e6f70aeb039416ea5f3279bfe0e50ee
Source dataset
uspto-grants-2008_12
Patent number
US07468367B2

Reaction notes

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