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 547029ノート

反応式

HRID 547029 の反応式
[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

参加物

9

反応物 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

生成物 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 Ester収率 97.1%

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

(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%).

後処理

  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)

出典と根拠

ORDレコード
ord-9f5b370cc00946aa98f5504bf4974961
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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