Potassium Phosphate, Tribasic → (4'-{1-ethyl-1-[4-((E)-3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-5-fluoro-biphenyl-3-yl)-acetic Acid Methyl Ester

HRID 547029Notes

Reaction equation

HRID 547029 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7](Cl)[CH:6]=1.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: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].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:6]=[C:7]([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:8]=[C:9]([F:11])[CH:10]=1

Participants

9

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57443518(3-chloro-5-fluoro-phenyl)-acetic Acid Methyl EsterHCID 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 57709075(4'-{1-ethyl-1-[4-((E)-3-ethyl-3-hydroxy-1-pentenyl)-3-methyl-phenyl]-propyl}-5-fluoro-biphenyl-3-yl)-acetic Acid Methyl EsterYield 97.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(3-Chloro-5-fluoro-phenyl)acetic acid methyl ester (Example 127-(1); 35 mg, 0.173 mmol), palladium acetate (2.7 mg, 0.012 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (9.4 mg, 0.023 mmol), potassium phosphate (73 mg, 0.345 mmol) and water (0.2 mL) were added to a solution of (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); 55 mg, 0.115 mmol) in toluene (2 mL). After replacement with nitrogen, the mixture was stirred at 100° C. for two hours. The reaction mixture was then poured into a saturated aqueous sodium bicarbonate solution, followed by extraction with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to give the target compound as a colorless oil (57.7 mg, 97%).

Workup

  1. extractionfollowed by extraction with dichloromethane
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-9f5b370cc00946aa98f5504bf4974961
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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