Potassium Phosphate, Tribasic → methyl (4'-{1-ethyl-1-[4-((E)-3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)-acetate

HRID 546891Notes

Reaction equation

HRID 546891 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](Cl)=[CH:7][C:6]=1[F:12].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:51]([C:53]([OH:86])([CH2:84][CH3:85])/[CH:54]=[CH: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].C(=O)(O)[O-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH2:63]([C:62]([C:65]1[CH:70]=[CH:69][C:68]([C:8]2[CH:9]=[CH:10][C:5]([CH2:4][C:3]([O:2][CH3:1])=[O:13])=[C:6]([F:12])[CH:7]=2)=[C:67]([CH3:80])[CH:66]=1)([C:59]1[CH:60]=[CH:61][C:56](/[CH:55]=[CH:54]/[C:53]([CH2:51][CH3:52])([OH:86])[CH2:84][CH3:85])=[C:57]([CH3:83])[CH:58]=1)[CH2:81][CH3:82])[CH3:64]

Participants

9

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57443493Methyl 2-(4-chloro-2-fluorophenyl)acetateHCID 57463789(E)-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)-1-penten-3-ol

Product 1

HCID 57709052methyl (4'-{1-ethyl-1-[4-((E)-3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-3-fluoro-2'-methyl-biphenyl-4-yl)-acetateYield 47%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(4-Chloro-2-fluoro-phenyl)acetic acid methyl ester (Example 40; 52 mg, 0.256 mmol), toluene (2.8 mL), palladium acetate (3.8 mg, 0.017 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (14 mg, 0.034 mmol), potassium phosphate (108 mg, 0.510 mmol) and water (0.28 mL) were added to (E)-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)-1-penten-3-ol (Example 28; 83.6 mg, 0.170 mmol), and the mixture was stirred in a nitrogen atmosphere at 100° C. for one hour. The reaction solution was poured into a saturated aqueous sodium bicarbonate solution, and then the aqueous layer was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (17% ethyl acetate/hexane) to give the title compound (42 mg, 47%).

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel chromatography (17% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-6dc2ec7eff104016ab7adec3413e3f0e
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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