Potassium Phosphate, Tribasic → [2-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2-methyl-phenyl)-thiazol-4-yl]-acetic Acid Ethyl Ester

HRID 546945Notes

Reaction equation

HRID 546945 reaction equation
[CH2:1]([C:3]([C:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([C:36]([F:39])([F:38])[F:37])([OH:35])[C:31]([F:34])([F:33])[F:32])=[C:24]([CH3:40])[CH:23]=1)([C:6]1[CH:11]=[CH:10][C:9](B2OC(C)(C)C(C)(C)O2)=[C:8]([CH3:21])[CH:7]=1)[CH2:4][CH3:5])[CH3:2].[CH2:41]([O:43][C:44](=[O:52])[CH2:45][C:46]1[N:47]=[C:48](Br)[S:49][CH:50]=1)[CH3:42].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.O>[CH2:41]([O:43][C:44](=[O:52])[CH2:45][C:46]1[N:47]=[C:48]([C:9]2[CH:10]=[CH:11][C:6]([C:3]([CH2:4][CH3:5])([C:22]3[CH:27]=[CH:26][C:25](/[CH:28]=[CH:29]/[C:30]([OH:35])([C:36]([F:38])([F:39])[F:37])[C:31]([F:34])([F:33])[F:32])=[C:24]([CH3:40])[CH:23]=3)[CH2:1][CH3:2])=[CH:7][C:8]=2[CH3:21])[S:49][CH:50]=1)[CH3:42]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 53428667Ethyl 2-(2-bromo-1,3-thiazol-4-yl)acetateHCID 57708964(E)-4-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1,1,1-trifluoro-2-trifluoromethyl-3-buten-2-ol

Product 1

HCID 57454139[2-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2-methyl-phenyl)-thiazol-4-yl]-acetic Acid Ethyl EsterYield 39.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Degassed N,N-dimethylformamide (0.25 mL) was added to (E)-4-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1,1,1-trifluoro-2-trifluoromethyl-3-buten-2-ol (Example 26-(5); 22.9 mg, 0.0401 mmol), (2-bromo-thiazol-4-yl)-acetic acid ethyl ester (Example 42; 17.8 mg, 0.071 mmol), tetrakis(triphenylphosphine)palladium (0) (5.9 mg, 0.0051 mmol) and potassium phosphate (19.2 mg, 0.0904 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 95 to 105° C. for five hours. Water was added to the reaction mixture, followed by extraction with diethyl ether. The extract was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/dichloromethane=1/4) to give the title compound (9.7 mg, 39%).

Workup

  1. customDegassed N,N-dimethylformamide (0.25 mL)
  2. temperatureAfter replacement with nitrogen, the mixture was heated
  3. extractionfollowed by extraction with diethyl ether
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (hexane/dichloromethane=1/4)

Sources & evidence

ORD record
ord-7626bed1b47e4eec9a9765eeef8179c8
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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