Water → 2-Methyl-2-({4-[2-({5-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl}oxy)ethyl]-1,3-thiazol-2-yl]thio}propionic acid tert-butyl ester

HRID 914323Notes

Reaction equation

HRID 914323 reaction equation
[C:1]([O:5][C:6](=[O:26])[C:7]([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][O:18][C:19]2[N:24]=[CH:23][C:22](Br)=[CH:21][N:20]=2)[N:15]=1)([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].[F:27][C:28]([F:41])([F:40])[O:29][C:30]1[CH:35]=[CH:34][C:33](OB(O)O)=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.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:26])[C:7]([CH3:9])([S:10][C:11]1[S:12][CH:13]=[C:14]([CH2:16][CH2:17][O:18][C:19]2[N:24]=[CH:23][C:22]([C:33]3[CH:32]=[CH:31][C:30]([O:29][C:28]([F:27])([F:40])[F:41])=[CH:35][CH:34]=3)=[CH:21][N:20]=2)[N:15]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 227270174-Trifluoromethoxyphenylboric acidHCID 597594452-[(4-{2-[(5-Bromopyrimidin-2-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester

Product 1

HCID 597594072-Methyl-2-({4-[2-({5-[4-(trifluoromethoxy)phenyl]pyrimidin-2-yl}oxy)ethyl]-1,3-thiazol-2-yl]thio}propionic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Under nitrogen atmosphere, 2-[(4-{2-[(5-bromopyrimidin-2-yl)oxy]ethyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (600 mg) synthesized in Example 110-1 and 4-trifluoromethoxyphenylboric acid (400 mg) were dissolved in dioxane (6 mL) and aqueous sodium carbonate solution (2 mol/L, 3 mL), tetrakis(triphenylphosphine)palladium (75 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=3:1) to give the title compound (600 mg) as a colorless oil.

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=3:1)

Sources & evidence

ORD record
ord-6727e231550e4790bbf6520687e5b6da
Source dataset
uspto-grants-2011_09
Patent number
US08026370B2

Reaction notes

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