Potassium Phosphate, Tribasic → [5-(4-{1-ethyl-1-[3-methyl-4-(4-trimethylsilanyloxy-tetrahydro-pyran-4-ylethynyl)-phenyl]-propyl}-2-methyl-phenyl)-pyridin-3-yl]-acetic Acid Methyl Ester

HRID 547044노트

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HRID 547044 반응식
[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:6]=[N:7][CH:8]=[C:9](Br)[CH:10]=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:71]1[CH:76]=[CH:75][C:74]([C:77]#[C:78][C:79]2([O:85][Si:86]([CH3:89])([CH3:88])[CH3:87])[CH2:84][CH2:83][O:82][CH2:81][CH2:80]2)=[C:73]([CH3:90])[CH:72]=1)([C:55]1[CH:60]=[CH:59][C:58](B2OC(C)(C)C(C)(C)O2)=[C:57]([CH3:70])[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:6]=[N:7][CH:8]=[C:9]([C:58]2[CH:59]=[CH:60][C:55]([C:52]([CH2:53][CH3:54])([C:71]3[CH:76]=[CH:75][C:74]([C:77]#[C:78][C:79]4([O:85][Si:86]([CH3:87])([CH3:89])[CH3:88])[CH2:84][CH2:83][O:82][CH2:81][CH2:80]4)=[C:73]([CH3:90])[CH:72]=3)[CH2:50][CH3:51])=[CH:56][C:57]=2[CH3:70])[CH:10]=1

참가 물질

9

반응물 5

HCID 62657Potassium Phosphate, TribasicHCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23398394Methyl 2-(5-bromopyridin-3-yl)acetateHCID 577090594-(4-{1-Ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenylethynyl)-4-trimethylsilanyloxy-tetrahydro-pyran

생성물 1

HCID 57709020[5-(4-{1-ethyl-1-[3-methyl-4-(4-trimethylsilanyloxy-tetrahydro-pyran-4-ylethynyl)-phenyl]-propyl}-2-methyl-phenyl)-pyridin-3-yl]-acetic Acid Methyl Ester수율 91%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

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온도
100 °C

실험 절차

(5-Bromo-pyridin-3-yl)acetic acid methyl ester (Example 24-(2); 40 mg, 0.173 mmol), palladium acetate (2.7 mg, 0.012 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (9.9 mg, 0.024 mmol), potassium phosphate (74 mg, 0.348 mmol) and water (0.2 mL) were added to a solution of 4-(4-{1-ethyl-1-[3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propyl}-2-methyl-phenylethynyl)-4-trimethylsilanyloxy-tetrahydro-pyran (Example 130-(4); 66.4 mg, 0.116 mmol) in toluene (3 mL). After replacement with nitrogen, the mixture was stirred at 100° C. for 3.5 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=1:1) to give the target compound as a colorless oil (62.9 mg, 91%).

후처리

  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=1:1)

출처 및 근거

ORD 기록
ord-f9f26f5aed8e4a58814c255b93771cdb
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07935688B2

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