Cesium carbonate → 1-[5-Chloro-8-(3-fluoropiperidin-1-yl)quinolin-7-yl]ethanone

HRID 1192602노트

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HRID 1192602 반응식
FC(F)(F)S(O[C:7]1[C:8]([C:18](=[O:20])[CH3:19])=[CH:9][C:10]([Cl:17])=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2)(=O)=O.Cl.[F:24][CH:25]1[CH2:30][CH2:29][CH2:28][NH:27][CH2:26]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>[Cl:17][C:10]1[CH:9]=[C:8]([C:18](=[O:20])[CH3:19])[C:7]([N:27]2[CH2:28][CH2:29][CH2:30][CH:25]([F:24])[CH2:26]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 27591563-FLUOROPIPERIDINE HYDROCHLORIDEHCID 58368658HCID 58368658, 화합물

생성물 1

HCID 583684891-[5-Chloro-8-(3-fluoropiperidin-1-yl)quinolin-7-yl]ethanone수율 28%

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-chloroquinolin-8-yl trifluoromethanesulfonate (0.12 g, 0.34 mmol, from Example 47, Step 2), 3-fluoropiperidine hydrochloride (0.057 g, 0.41 mmol), palladium acetate (1.5 mg, 0.0068 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (6.3 mg, 0.010 mmol), and cesium carbonate (0.31 g, 0.95 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 MgSO4 and evaporated to dryness. The residue was purified on silica gel (eluting with 0 to 5% methanol in dichloromethane) to give the desired product (28.7 mg, 28%). LCMS calculated for C16H17ClFN2O (M+H)+: m/z=307.1; Found 307.0.

후처리

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washThe filtrate was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe residue was purified on silica gel (eluting with 0 to 5% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-c6b09a1d716e4510a388d78237fcebc5
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08680108B2

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