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

HRID 546998Notes

Reaction equation

HRID 546998 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:86])([CH2:84][CH3:85])[CH2:54][CH2:55][C:56]1[CH:61]=[CH:60][C:59]([C:62]([CH2:81][CH3:82])([C:65]2[CH:70]=[CH:69][C:68](B3OC(C)(C)C(C)(C)O3)=[C:67]([CH3:80])[CH:66]=2)[CH2:63][CH3:64])=[CH:58][C:57]=1[CH3:83])[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:69]=[CH:70][C:65]([C:62]([CH2:63][CH3:64])([C:59]3[CH:60]=[CH:61][C:56]([CH2:55][CH2:54][C:53]([CH2:84][CH3:85])([OH:86])[CH2:51][CH3:52])=[C:57]([CH3:83])[CH:58]=3)[CH2:81][CH3:82])=[CH:66][C:67]=2[CH3:80])=[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 577091063-Ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-pentan-3-ol

Product 1

HCID 57708950(4'-{1-Ethyl-1-[4-(3-ethyl-3-hydroxy-pentyl)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)acetic acid methyl esterYield 70.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
100 °C

Procedure

A solution of palladium acetate (3.1 mg, 0.0139 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (11.4 mg, 0.0279 mmol) and potassium phosphate (59.3 mg, 0.0279 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; 30.3 mg, 0.14 mmol) and 3-ethyl-1-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-pentan-3-ol (Example 29; 49.2 mg, 0.0998 mmol) in toluene (0.250 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 thin layer silica gel chromatography (15% ethyl acetate/hexane) to give the title compound (37.5 mg, 70%).

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 (15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a2b64c1cd3ba44548b8d627ee5a07d99
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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