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

HRID 546950Notes

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]([C:78]1[CH:83]=[CH:82][C:81](B2OC(C)(C)C(C)(C)O2)=[C:80]([CH3:93])[CH:79]=1)([C:56]1[CH:61]=[CH:60][C:59]([C:62]#[C:63][C:64]([O:73][CH2:74][O:75][CH3:76])([C:69]([F:72])([F:71])[F:70])[C:65]([F:68])([F:67])[F:66])=[C:58]([CH3:77])[CH:57]=1)[CH2:54][CH3:55])[CH3:52].C(=O)(O)[O-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:81]2[CH:82]=[CH:83][C:78]([C:53]([CH2:54][CH3:55])([C:56]3[CH:61]=[CH:60][C:59]([C:62]#[C:63][C:64]([O:73][CH2:74][O:75][CH3:76])([C:69]([F:72])([F:71])[F:70])[C:65]([F:68])([F:67])[F:66])=[C:58]([CH3:77])[CH:57]=3)[CH2:51][CH3:52])=[CH:79][C:80]=2[CH3:93])=[CH:7][C:6]=1[F:12]

Participants

Conditions

Temperature: 100 °C

Procedure

(4-Chloro-2-fluoro-phenyl)acetic acid methyl ester (Example 40; 37.2 mg, 0.183 mmol), toluene (2.0 mL), palladium acetate (2.7 mg, 0.012 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (10.0 mg, 0.0244 mmol), potassium phosphate (78 mg, 0.3666 mmol) and water (0.200 mL) were added to 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); 75 mg, 0.122 mmol), and the mixture was stirred in a nitrogen atmosphere at 100° C. for 1.5 hours. 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 containing (4-chloro-2-fluoro-phenyl)acetic acid methyl ester (41 mg, 52%).

Workup

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

Sources & evidence

ORD record: ord-a0d8354cf7c44248ada299930b25aa4a
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07935688B2

Reaction notes

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