Potassium Phosphate, Tribasic → (4'-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2'-methyl-biphenyl-4-yl)acetic acid methyl ester

HRID 546887Notes

Reaction equation

HRID 546887 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:38]([C:40]([C:59]1[CH:64]=[CH:63][C:62](/[CH:65]=[CH:66]/[C:67]([C:73]([F:76])([F:75])[F:74])([OH:72])[C:68]([F:71])([F:70])[F:69])=[C:61]([CH3:77])[CH:60]=1)([C:43]1[CH:48]=[CH:47][C:46](B2OC(C)(C)C(C)(C)O2)=[C:45]([CH3:58])[CH:44]=1)[CH2:41][CH3:42])[CH3:39].[CH3:78][O:79][C:80](=[O:89])[CH2:81][C:82]1[CH:87]=[CH:86][C:85](Br)=[CH:84][CH:83]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:78][O:79][C:80](=[O:89])[CH2:81][C:82]1[CH:87]=[CH:86][C:85]([C:46]2[CH:47]=[CH:48][C:43]([C:40]([CH2:41][CH3:42])([C:59]3[CH:64]=[CH:63][C:62](/[CH:65]=[CH:66]/[C:67]([OH:72])([C:73]([F:75])([F:76])[F:74])[C:68]([F:71])([F:70])[F:69])=[C:61]([CH3:77])[CH:60]=3)[CH2:38][CH3:39])=[CH:44][C:45]=2[CH3:58])=[CH:84][CH:83]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 316783Methyl 2-(4-bromophenyl)acetateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 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 57709022(4'-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2'-methyl-biphenyl-4-yl)acetic acid methyl esterYield 34%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Palladium acetate (3.6 mg, 0.016 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (13.1 mg, 0.032 mmol), potassium phosphate (51 mg, 0.24 mmol) and water (0.04 mL) were added to a solution of (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); 40 mg, 0.070 mmol) and (4-bromo-phenyl)acetic acid methyl ester (Tetrahedron Letters 44 (2003) 331-334; 28 mg, 0.122 mmol) in toluene (0.4 mL). After replacement with nitrogen, the mixture was stirred at 100° C. for 30 minutes. Then, the reaction mixture was concentrated under reduced pressure, and the residue was dissolved in dichloromethane. Thereafter, the solution was filtered through amino silica gel, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=2:1) to give the target compound as a colorless oil (14.1 mg, 34%).

Workup

  1. concentrationThen, the reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in dichloromethane
  3. filtrationThereafter, the solution was filtered through amino silica gel
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-7c0149b6738e4172805a9045abe8a179
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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