Potassium Phosphate, Tribasic → [5-(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 Methyl Ester

HRID 546943Notes

Reaction equation

HRID 546943 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:38][O:39][C:40](=[O:49])[CH2:41][C:42]1[CH:43]=[N:44][CH:45]=[C:46](Br)[CH:47]=1.[CH2:50]([C:52]([C:71]1[CH:76]=[CH:75][C:74](/[CH:77]=[CH:78]/[C:79]([C:85]([F:88])([F:87])[F:86])([OH:84])[C:80]([F:83])([F:82])[F:81])=[C:73]([CH3:89])[CH:72]=1)([C:55]1[CH:60]=[CH:59][C:58](B2OC(C)(C)C(C)(C)O2)=[C:57]([CH3:70])[CH:56]=1)[CH2:53][CH3:54])[CH3:51]>O.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:38][O:39][C:40](=[O:49])[CH2:41][C:42]1[CH:43]=[N:44][CH:45]=[C:46]([C:58]2[CH:59]=[CH:60][C:55]([C:52]([CH2:53][CH3:54])([C:71]3[CH:76]=[CH:75][C:74](/[CH:77]=[CH:78]/[C:79]([OH:84])([C:85]([F:87])([F:88])[F:86])[C:80]([F:83])([F:82])[F:81])=[C:73]([CH3:89])[CH:72]=3)[CH2:50][CH3:51])=[CH:56][C:57]=2[CH3:70])[CH:47]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23398394Methyl 2-(5-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 57454137[5-(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 Methyl EsterYield 17.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

A solution of palladium acetate (1.4 mg, 0.00623 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (5.3 mg, 0.0124 mmol) and potassium phosphate (27.6 mg, 0.1246 mmol) in water (0.020 mL) and toluene (0.100 mL) was stirred for three minutes. Then, a solution of (5-bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 15.2 mg, 0.0659 mmol) and (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); 26.9 mg, 0.0471 mmol) in toluene (0.12 mL) was added, and the mixture was stirred in a nitrogen atmosphere at 100° C. for one hour. After filtration through cotton plug, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate=3/2) to give the title compound (5.0 mg, 17%).

Workup

  1. filtrationAfter filtration through cotton plug
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate=3/2)

Sources & evidence

ORD record
ord-5dbcbb2bf8fd4dc0a89432ba7187b30d
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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