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

HRID 547014Notes

Reaction equation

HRID 547014 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]([OH:85])([CH2:83][CH3:84])/[CH:54]=[CH:55]/[C:56]1[CH:61]=[CH:60][C:59]([C:62]([CH2:80][CH3:81])([C:65]2[CH:70]=[CH:69][C:68](B3OC(C)(C)C(C)(C)O3)=[CH:67][CH:66]=2)[CH2:63][CH3:64])=[CH:58][C:57]=1[CH3:82])[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:68]2[CH:67]=[CH:66][C:65]([C:62]([CH2:80][CH3:81])([C:59]3[CH:60]=[CH:61][C:56](/[CH:55]=[CH:54]/[C:53]([CH2:83][CH3:84])([OH:85])[CH2:51][CH3:52])=[C:57]([CH3:82])[CH:58]=3)[CH2:63][CH3:64])=[CH:70][CH:69]=2)=[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 57708914(E)-3-ethyl-1-(4-{1-ethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-penten-3-ol

Product 1

HCID 57709138(E)-(4'-{1-ethyl-1-[4-(3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-3-fluoro-biphenyl-4-yl)-acetic Acid Methyl EsterYield 74%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A solution of palladium acetate (3.3 mg, 0.0146 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (12.0 mg, 0.0293 mmol) and potassium phosphate (62.3 mg, 0.29 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; 31.8 mg, 0.15 mmol) and (E)-3-ethyl-1-(4-{1-ethyl-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1-penten-3-ol (Example 39-(5); 50.0 mg, 0.1049 mmol) in toluene (0.250 mL) was added, and the mixture was stirred in a nitrogen atmosphere at 100° C. for 1.5 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 (40.1 mg, 73%).

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-db91b2f577d4429ea9fcf9ab2a54ccf4
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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