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Water → 2-Methyl-2-({4-[({[4'-(trifluoromethyl)biphenyl-4-yl]carbonyl}amino)methyl]-1,3-thiazol-2-yl}thio)propionic acid tert-butyl ester

HRID 914383
Notes
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Reaction equation

HRID 914383 reaction equation
[C:1]([O:5][C:6](=[O:27])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][NH:17][C:18](=[O:26])[C:19]2[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=2)[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[F:28][C:29]([F:41])([F:40])[C:30]1[CH:35]=[CH:34][C:33](OB(O)O)=[CH:32][CH:31]=1.O>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].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>[C:1]([O:5][C:6](=[O:27])[C:7]([CH3:9])([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][NH:17][C:18]([C:19]2[CH:24]=[CH:23][C:22]([C:33]3[CH:34]=[CH:35][C:30]([C:29]([F:41])([F:40])[F:28])=[CH:31][CH:32]=3)=[CH:21][CH:20]=2)=[O:26])[N:15]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 962WaterHCID 17793420p-Trifluoromethylphenylboric acidHCID 597592672-[(4-{[(4-Bromobenzoyl)amino]methyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

Product 1

HCID 597591922-Methyl-2-({4-[({[4'-(trifluoromethyl)biphenyl-4-yl]carbonyl}amino)methyl]-1,3-thiazol-2-yl}thio)propionic acid tert-butyl esterYield 86.4%

Reagents, catalysts & solvents 3

HCID 178418397
HCID 178418397, compound
Catalyst
HCID 10340Sodium CarbonateSolvent
HCID 312751,4-DioxaneSolvent

Procedure

Under nitrogen atmosphere, 2-[(4-{[(4-bromobenzoyl)amino]methyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (600 mg) synthesized in Example 455-1 and 4-trifluoromethylphenylboric acid (363 mg) were dissolved in dioxane (8 mL) and 2 M aqueous sodium carbonate solution (4 mL), tetrakis(triphenylphosphine)palladium (73 mg) was added, and the mixture was refluxed for 4 hr. The reaction mixture was cooled, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=2:1 to 1:1) to give the title compound (590 mg) as a white solid.

Workup

  1. temperaturethe mixture was refluxed for 4 hr
  2. temperatureThe reaction mixture was cooled
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate=2:1 to 1:1)

Sources & evidence

ORD record
ord-cf24585153be41b8abfdd4cf699c107d
Source dataset
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08026370B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes