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 546950ノート

反応式

HRID 546950 の反応式
[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]

参加物

9

反応物 5

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

生成物 1

HCID 57709061(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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

(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%).

後処理

  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)

出典と根拠

ORDレコード
ord-a0d8354cf7c44248ada299930b25aa4a
出典データセット
uspto-grants-2011_05
特許番号
US07935688B2

反応ノート

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