Potassium Phosphate, Tribasic → (4'-{1-Ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)acetic acid methyl ester

HRID 546983Notes

Reaction equation

HRID 546983 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:50])[CH2:41][C:42]1[CH:47]=[CH:46][C:45](Cl)=[CH:44][C:43]=1[F:49].[CH2:51]([C:53]([C:72]1[CH:85]=[CH:84][C:75]([O:76][CH2:77][CH:78]([OH:83])[C:79]([CH3:82])([CH3:81])[CH3:80])=[C:74]([CH3:86])[CH:73]=1)([C:56]1[CH:61]=[CH:60][C:59](B2OC(C)(C)C(C)(C)O2)=[C:58]([CH3:71])[CH:57]=1)[CH2:54][CH3:55])[CH3:52]>O.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:38][O:39][C:40](=[O:50])[CH2:41][C:42]1[CH:47]=[CH:46][C:45]([C:59]2[CH:60]=[CH:61][C:56]([C:53]([CH2:51][CH3:52])([C:72]3[CH:85]=[CH:84][C:75]([O:76][CH2:77][CH:78]([OH:83])[C:79]([CH3:81])([CH3:82])[CH3:80])=[C:74]([CH3:86])[CH:73]=3)[CH2:54][CH3:55])=[CH:57][C:58]=2[CH3:71])=[CH:44][C:43]=1[F:49]

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57443493Methyl 2-(4-chloro-2-fluorophenyl)acetateHCID 577089691-(4-{1-Ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenoxy)-3,3-dimethyl-butan-2-ol

Product 1

HCID 57708937(4'-{1-Ethyl-1-[4-(2-hydroxy-3,3-dimethyl-butoxy)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)acetic acid methyl esterYield 32.9%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A solution of palladium acetate (3.8 mg, 0.0169 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (13.9 mg, 0.0339 mmol) and potassium phosphate (72.0 mg, 0.33 mmol) in water (0.050 mL) and toluene (0.200 mL) was stirred for three minutes. A solution of (4-chloro-2-fluoro-phenyl)acetic acid methyl ester (Example 40; 36.8 mg, 0.18 mmol) and 1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenoxy)-3,3-dimethyl-butan-2-ol (Example 31; 60.0 mg, 0.12 mmol) in toluene (0.3 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 thin layer silica gel chromatography (8% ethyl acetate/hexane) to give the title compound (21.1 mg, 32%).

Workup

  1. filtrationAfter filtration through cotton plug
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by thin layer silica gel chromatography (8% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9c57c60b6bb34f9b908d34528105619a
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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