1,4-Dioxane → 1-((3R,4R)-3-hydroxy-4-(4-methoxy-6-methylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

HRID 1666623노트

반응식

HRID 1666623 반응식
Cl[C:2]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH3:14])[CH:8]=2)[N:3]=1.[NH2:15][C@H:16]1[C@H:20]([OH:21])[CH2:19][N:18]([C:22](=[O:35])[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][C:31]([F:34])([F:33])[F:32])=[CH:26][CH:25]=2)[CH2:17]1.O1CCOCC1.CC(C)([O-])C.[Na+]>C(OCC)(=O)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:21][C@H:20]1[C@H:16]([NH:15][C:2]2[CH:11]=[C:10]([O:12][CH3:13])[C:9]3[C:4](=[CH:5][CH:6]=[C:7]([CH3:14])[CH:8]=3)[N:3]=2)[CH2:17][N:18]([C:22](=[O:35])[CH2:23][C:24]2[CH:25]=[CH:26][C:27]([O:30][C:31]([F:32])([F:33])[F:34])=[CH:28][CH:29]=2)[CH2:19]1

참가 물질

8

반응물 4

HCID 312751,4-DioxaneHCID 183537192-Chloro-4-methoxy-6-methylquinolineHCID 23676156Sodium t-butoxideHCID 579701111-((3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone

생성물 1

HCID 579701171-((3R,4R)-3-hydroxy-4-(4-methoxy-6-methylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone수율 58.2%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

반응 조건

온도
70 °C

실험 절차

To a mixture of 2-chloro-4-methoxy-6-methylquinoline (0.12 g), Pd2(dba)3 (0.027 g), (±)-BINAP (0.056 g), 1-((3R,4R)-3-amino-4-hydroxypyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.22 g), and 1,4-dioxane (2 mL) was added sodium t-butoxide (0.17 g) under nitrogen atmosphere, and the mixture was stirred at 70° C. for 1 h. The reaction mixture was diluted with ethyl acetate and water, then the interlayer was removed by Celite filtration, and the organic layer was washed with saturated brine. The organic layer was dried with anhydrous magnesium sulfate, the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (silica gel, ethyl acetate, and NH silica gel, ethyl acetate/chloroform) to obtain white solid 1-((3R,4R)-3-hydroxy-4-(4-methoxy-6-methylquinolin-2-ylamino)pyrrolidin-1-yl)-2-(4-trifluoromethoxyphenyl)ethanone (0.16 g).

후처리

  1. customthe interlayer was removed by Celite filtration
  2. washthe organic layer was washed with saturated brine
  3. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  4. customthe desiccant was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (silica gel, ethyl acetate, and NH silica gel, ethyl acetate/chloroform)

출처 및 근거

ORD 기록
ord-25d8a4f58f144c97ba50bf9cff98c21a
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044068B2

반응 노트

불러오는 중…