Potassium Phosphate, Tribasic → (4'-{1-Ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-1-butynyl)-phenyl]-propyl}-2'-methyl-biphenyl-4-yl)acetic acid methyl ester

HRID 546884Notes

Reaction equation

HRID 546884 reaction equation
[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:50]([C:52]([C:77]1[CH:82]=[CH:81][C:80](B2OC(C)(C)C(C)(C)O2)=[C:79]([CH3:92])[CH:78]=1)([C:55]1[CH:60]=[CH:59][C:58]([C:61]#[C:62][C:63]([O:72][CH2:73][O:74][CH3:75])([C:68]([F:71])([F:70])[F:69])[C:64]([F:67])([F:66])[F:65])=[C:57]([CH3:76])[CH:56]=1)[CH2:53][CH3:54])[CH3:51].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:12])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:80]2[CH:81]=[CH:82][C:77]([C:52]([CH2:53][CH3:54])([C:55]3[CH:60]=[CH:59][C:58]([C:61]#[C:62][C:63]([O:72][CH2:73][O:74][CH3:75])([C:68]([F:71])([F:70])[F:69])[C:64]([F:67])([F:66])[F:65])=[C:57]([CH3:76])[CH:56]=3)[CH2:50][CH3:51])=[CH:78][C:79]=2[CH3:92])=[CH:7][CH:6]=1

Participants

9

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 316783Methyl 2-(4-bromophenyl)acetateHCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 577089482-(4-{1-Ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-1-butynyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane

Product 1

HCID 57709204(4'-{1-Ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-1-butynyl)-phenyl]-propyl}-2'-methyl-biphenyl-4-yl)acetic acid methyl esterYield 86.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

(4-Bromo-phenyl)acetic acid methyl ester (Tetrahedron Letters 44 (2003) 331-334; 28 mg, 0.122 mmol), palladium acetate (1.8 mg, 0.008 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (6.6 mg, 0.016 mmol), potassium phosphate (52 mg, 0.246 mmol) and water (0.1 mL) were added to a solution of 2-(4-{1-ethyl-1-[3-methyl-4-(4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-1-butynyl)-phenyl]-propyl}-2-methyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Example 25-(4); 50 mg, 0.082 mmol) in toluene (1 mL). After replacement with nitrogen, the mixture was stirred at 100° C. for one hour. 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 (44.9 mg, 86%).

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-e8f61c92b835462dab8efdae39e51e96
Source dataset
uspto-grants-2011_05
Patent number
US07935688B2

Reaction notes

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