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Dimethylformamide → ethyl 1-{[(5-{3-fluoro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylate

HRID 623912
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HRID 623912 반응식
CN(C)C=O.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=2)=[C:9]([F:30])[CH:8]=1.[CH3:31][C:32]1[C:37](B2OC(C)(C)C(C)(C)O2)=[CH:36][N:35]=[C:34]([O:47][CH2:48][C:49]2([C:53]([O:55][CH2:56][CH3:57])=[O:54])[CH2:52][CH2:51][CH2:50]2)[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+]>O.C(OCC)(=O)C>[F:30][C:9]1[CH:8]=[C:7]([C:37]2[C:32]([CH3:31])=[CH:33][C:34]([O:47][CH2:48][C:49]3([C:53]([O:55][CH2:56][CH3:57])=[O:54])[CH2:52][CH2:51][CH2:50]3)=[N:35][CH:36]=2)[CH:12]=[CH:11][C:10]=1[C:13]1[N:14]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=1
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참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 679752622-(4-bromo-2-fluorophenyl)-4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazoleHCID 67975298Ethyl 1-(((4-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl)oxy)methyl)cyclobutanecarboxylate

생성물 1

HCID 86698178
ethyl 1-{[(5-{3-fluoro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylate
수율 78.1%

시약·촉매·용매 2

HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
65 °C

실험 절차

N,N-dimethylformamide (5 mL) was added to 2-(4-bromo-2-fluorophenyl)-4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole (293 mg), ethyl 1-({[4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]oxy}methyl)-cyclobutanecarboxylate (250 mg) and palladium chloride (dppf) methylene chloride complex (28 mg), and after adding 2N aqueous sodium carbonate solution (1 mL) to the mixture, the atmosphere was replaced with nitrogen and the mixture was stirred at 65° C. for 3 hours. To the reaction mixture were added ethyl acetate and water to extract the objective compound. The organic layer was washed with a saturated brine, and dried over anhydrous magnesium sulfate. After concentrating the mixture under reduced pressure, the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 80:20) to obtain ethyl 1-{[(5-{3-fluoro-4-[4-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl]phenyl}-4-methylpyridin-2-yl)oxy]methyl}cyclobutanecarboxylate (316 mg).

후처리

  1. extractionto extract the objective compound
  2. washThe organic layer was washed with a saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationAfter concentrating the mixture under reduced pressure
  5. customthe obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=100:0 to 80:20)

출처 및 근거

ORD 기록
ord-fd918965c17d4e73bd835197885ae3c7
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09302996B2

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