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Dimethylformamide → tert-butyl {(1S)-2-[(6-{6-[(3,3-difluorocyclobutyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate

HRID 1026348
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HRID 1026348 반응식
[F:1][C:2]1[CH:3]=[C:4]([O:18][CH2:19][C@@H:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:21])[CH:5]=[N:6][C:7]=1[C:8]1[O:9][C:10]2[CH:16]=[C:15]([OH:17])[CH:14]=[CH:13][C:11]=2[N:12]=1.CS(O[CH2:35][CH:36]1[CH2:39][C:38]([F:41])([F:40])[CH2:37]1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[F:40][C:38]1([F:41])[CH2:39][CH:36]([CH2:35][O:17][C:15]2[CH:14]=[CH:13][C:11]3[N:12]=[C:8]([C:7]4[N:6]=[CH:5][C:4]([O:18][CH2:19][C@@H:20]([NH:22][C:23](=[O:29])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH3:21])=[CH:3][C:2]=4[F:1])[O:9][C:10]=3[CH:16]=2)[CH2:37]1
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참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 11430Potassium Carbonate2회HCID 58223412(3,3-difluorocyclobutyl)methyl methanesulfonate2회HCID 136372365tert-butyl [(1S)-2-{[5-fluoro-6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate

생성물 1

HCID 86666323
tert-butyl {(1S)-2-[(6-{6-[(3,3-difluorocyclobutyl)methoxy]-1,3-benzoxazol-2-yl}-5-fluoropyridin-3-yl)oxy]-1-methylethyl}carbamate
수율 80.5%

시약·촉매·용매 1

HCID 962Water용매

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온도
60 °C

실험 절차

A mixture of tert-butyl [(1S)-2-{[5-fluoro-6-(6-hydroxy-1,3-benzoxazol-2-yl)pyridin-3-yl]oxy}-1-methylethyl]carbamate (770 mg), (3,3-difluorocyclobutyl)methyl methanesulfonate (459 mg), potassium carbonate (317 mg), and DMF (10 mL) was stirred at 60° C. for 2 hr. Then additional (3,3-difluorocyclobutyl)methyl methanesulfonate (459 mg) and potassium carbonate (317 mg) were added, and the mixture was stirred at 60° C. overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (780 mg) as a white solid.

후처리

  1. stirringthe mixture was stirred at 60° C. overnight
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-8e873510338f45ff87df204c07ac6ce7
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08729102B2

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