Potassium Phosphate, Tribasic → (3-chloro-4'-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2'-methyl-biphenyl-4-yl)acetic acid methyl ester

HRID 546938노트

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HRID 546938 반응식
[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[Cl: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:72]1[CH:77]=[CH:76][C:75](/[CH:78]=[CH:79]/[C:80]([C:86]([F:89])([F:88])[F:87])([OH:85])[C:81]([F:84])([F:83])[F:82])=[C:74]([CH3:90])[CH:73]=1)([C:56]1[CH:61]=[CH:60][C:59](B2OC(C)(C)C(C)(C)O2)=[C:58]([CH3:71])[CH:57]=1)[CH2:54][CH3:55])[CH3:52]>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:10]=[CH:9][C:8]([C:59]2[CH:60]=[CH:61][C:56]([C:53]([CH2:54][CH3:55])([C:72]3[CH:77]=[CH:76][C:75](/[CH:78]=[CH:79]/[C:80]([OH:85])([C:86]([F:88])([F:89])[F:87])[C:81]([F:84])([F:83])[F:82])=[C:74]([CH3:90])[CH:73]=3)[CH2:51][CH3:52])=[CH:57][C:58]=2[CH3:71])=[CH:7][C:6]=1[Cl:12]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 2734106Methyl 2,4-dichlorobenzeneacetateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 57708964(E)-4-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1,1,1-trifluoro-2-trifluoromethyl-3-buten-2-ol

생성물 1

HCID 57708925(3-chloro-4'-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2'-methyl-biphenyl-4-yl)acetic acid methyl ester수율 7.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

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온도
100 °C

실험 절차

(2,4-Dichloro-phenyl)acetic acid methyl ester (Example 41; 28.7 mg, 0.131 mmol), palladium acetate (2.0 mg, 0.009 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (7.2 mg, 0.018 mmol), potassium phosphate (56 mg, 0.263 mmol) and water (0.1 mL) were added to a solution of (E)-4-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenyl)-1,1,1-trifluoro-2-trifluoromethyl-3-buten-2-ol (Example 26-(5); 50 mg, 0.088 mmol) in toluene (1 mL). After replacement with nitrogen, the mixture was stirred at 100° C. overnight. Then, the reaction mixture was filtered through amino silica gel, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=2:1) to give the target compound as a colorless oil (3.9 mg, 7%).

후처리

  1. filtrationThen, the reaction mixture was filtered through amino silica gel
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=2:1)

출처 및 근거

ORD 기록
ord-11fa024d91c44a5d9f56ff8ade2419cf
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935688B2

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