Cesium carbonate → 1-{5-Fluoro-8-[(3R)-3-hydroxypyrrolidin-1-yl]quinolin-7-yl}ethanone

HRID 1192578노트

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HRID 1192578 반응식
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([F:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.[NH:23]1[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCCC1.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:23]2[CH2:27][CH2:26][C@@H:25]([OH:28])[CH2:24]2)=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2759337(R)-3-PyrrolidinolHCID 583685787-Acetyl-5-fluoroquinolin-8-yl trifluoromethanesulfonate

생성물 1

HCID 583684551-{5-Fluoro-8-[(3R)-3-hydroxypyrrolidin-1-yl]quinolin-7-yl}ethanone수율 12.1%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

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온도
65 °C

실험 절차

A stirred mixture of 7-acetyl-5-fluoroquinolin-8-yl trifluoromethanesulfonate (0.101 g, 0.301 mmol), (3R)-pyrrolidin-3-ol (0.0315 g, 0.362 mmol), palladium acetate (1 mg, 0.006 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6 mg, 0.009 mmol), and cesium carbonate (0.147 g, 0.451 mmol) in tetrahydrofuran (3 mL) was heated at 65° C. overnight. The mixture was cooled, diluted with dichloromethane and filtered. The filtrate was washed with brine, dried over sodium sulfate and evaporated to dryness. The resulting residue was purified on silica gel, eluting with 0 to 10% MeOH in dichloromethane, to give the desired product (10 mg, 10%). LCMS calculated for C15H16FN2O2 (M+H)±: m/z=275.1; Found: 275.1.

후처리

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated to dryness
  6. customThe resulting residue was purified on silica gel
  7. washeluting with 0 to 10% MeOH in dichloromethane

출처 및 근거

ORD 기록
ord-0d09e80ce5db4c01a2ecd2b73beff894
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680108B2

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