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Water → Methyl 2-(4-(4'-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate

HRID 881733
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HRID 881733 반응식
[CH3:1][C:2]1[O:3][C:4]([C:25]([F:28])([F:27])[F:26])=[C:5]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:12][CH:11]=2)=[O:8])[N:6]=1.Br[C:30]1[CH:35]=[CH:34][C:33]([C:36]23[CH2:43][CH2:42][C:39]([CH2:44][C:45]([O:47][CH3:48])=[O:46])([CH2:40][CH2:41]2)[O:38][CH2:37]3)=[CH:32][CH:31]=1.O.[F-].[Cs+]>O1CCOCC1.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH3:1][C:2]1[O:3][C:4]([C:25]([F:26])([F:27])[F:28])=[C:5]([C:7]([NH:9][C:10]2[CH:11]=[CH:12][C:13]([C:30]3[CH:31]=[CH:32][C:33]([C:36]45[CH2:41][CH2:40][C:39]([CH2:44][C:45]([O:47][CH3:48])=[O:46])([CH2:42][CH2:43]4)[O:38][CH2:37]5)=[CH:34][CH:35]=3)=[CH:14][CH:15]=2)=[O:8])[N:6]=1
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참가 물질

7

반응물 4

HCID 962WaterHCID 25953Cesium fluorideHCID 86700823Methyl 2-(4-(4-bromophenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetateHCID 867008372-methyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(trifluoromethyl)oxazole-4-carboxamide

생성물 1

HCID 86700838Methyl 2-(4-(4'-(2-methyl-5-(trifluoromethyl)oxazole-4-carboxamido)-[1,1'-biphenyl]-4-yl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate
수율 50%

시약·촉매·용매 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

To a mixture of 2-methyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5-(trifluoromethyl)oxazole-4-carboxamide (300 mg, 0.757 mmol) and methyl 2-(4-(4-bromophenyl)-2-oxabicyclo[2.2.2]octan-1-yl)acetate (257 mg, 0.757 mmol) in dioxane (3 ml) was added H2O (0.33 ml) at room temperature. CsF (345 mg, 2.272 mmol) and Pd(amphos)Cl2 (53.6 mg, 0.076 mmol) were added and the mixture was degassed several times before being heated to 90° C. for overnight. The reaction mixture was cooled to room temperature and directly purified by column chromatography to afford the title compound as white solid after drying (200 mg, 50% yield). LC/MS, ESI-MS(+): 529.0, RT: 1.52 (Condition E).

후처리

  1. customthe mixture was degassed several times
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customdirectly purified by column chromatography

출처 및 근거

ORD 기록
ord-64412e2ef876479b88d45b5caf1b701a
출처 데이터셋
uspto-grants-2015_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08993619B2

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