Potassium Phosphate, Tribasic → [6-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2-methyl-phenyl)-pyridin-3-yl]-acetic Acid Ethyl Ester

HRID 546941Notes

Reaction equation

HRID 546941 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:53])[CH2:45][C:46]1[CH:47]=[CH:48][C:49](Br)=[N:50][CH:51]=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:53])[CH2:45][C:46]1[CH:51]=[N:50][C:49]([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:37])([F:39])[F:38])[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])=[CH:48][CH:47]=1)[CH3:42]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 57443504Ethyl 2-(6-bromopyridin-3-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 57454136[6-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2-methyl-phenyl)-pyridin-3-yl]-acetic Acid Ethyl EsterYield 80.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Degassed N,N-dimethylformamide (0.15 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); 14.0 mg, 0.0245 mmol), (2-bromo-pyridin-5-yl)acetic acid ethyl ester (Example 74-(1); 10.5 mg, 0.043 mmol), tetrakis(triphenylphosphine)palladium (0) (3.5 mg, 0.0030 mmol) and potassium phosphate (13.4 mg, 0.0631 mmol). After replacement with nitrogen, the mixture was heated while stirring at an external temperature of 85 to 95° C. for 10 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/ethyl acetate=3/1) to give the title compound (12 mg, 80%).

Workup

  1. customDegassed N,N-dimethylformamide (0.15 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/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-4a4c9cba97cd4da19cafeb48df9305de
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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