Potassium Phosphate, Tribasic → [4'-(1-ethyl-1-{4-[2-(1-hydroxy-cyclopentyl)-ethyl]-3-methyl-phenyl}-propyl)-3-fluoro-2'-methyl-biphenyl-4-yl]-acetic Acid Methyl Ester

HRID 547002Notes

Reaction equation

HRID 547002 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:77]=[CH:76][C:75]([CH2:78][CH2:79][C:80]2([OH:85])[CH2:84][CH2:83][CH2:82][CH2:81]2)=[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]([CH2:54][CH3:55])([C:72]3[CH:77]=[CH:76][C:75]([CH2:78][CH2:79][C:80]4([OH:85])[CH2:81][CH2:82][CH2:83][CH2:84]4)=[C:74]([CH3:86])[CH:73]=3)[CH2:51][CH3:52])=[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 57709074HCID 57709074, compound

Product 1

HCID 57709070[4'-(1-ethyl-1-{4-[2-(1-hydroxy-cyclopentyl)-ethyl]-3-methyl-phenyl}-propyl)-3-fluoro-2'-methyl-biphenyl-4-yl]-acetic Acid Methyl EsterYield 77%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A solution of palladium acetate (2.6 mg, 0.0114 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (9.4 mg, 0.0228 mmol) and potassium phosphate (48.4 mg, 0.22 mmol) in water (0.040 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; 24.7 mg, 0.12 mmol) and 1-[2-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-ethyl]-cyclopentanol (Example 40; 40.0 mg, 0.0815 mmol) in toluene (0.200 mL) was added, and the mixture was stirred in a nitrogen atmosphere at 100° C. for three hours. After filtration through cotton plug, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (17% ethyl acetate/hexane) to give the title compound (30.9 mg, 77%).

Workup

  1. filtrationAfter filtration through cotton plug
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel chromatography (17% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3b22e6d3c6d34f5ab691f3b164532901
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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