Cesium carbonate → Ethyl 2-[3-(ethylsulfanyl)phenoxy]-5-fluoronicotinate

HRID 724284노트

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HRID 724284 반응식
Cl[C:2]1[N:12]=[CH:11][C:10]([F:13])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH2:14]([S:16][C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1)[CH3:15].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[CH2:7]([O:6][C:4](=[O:5])[C:3]1[CH:9]=[C:10]([F:13])[CH:11]=[N:12][C:2]=1[O:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([S:16][CH2:14][CH3:15])[CH:18]=1)[CH3:8]

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 11390082Ethyl 2-chloro-5-fluoronicotinateHCID 129052213-(Ethylsulfanyl)phenol

생성물 1

HCID 21877167Ethyl 2-[3-(ethylsulfanyl)phenoxy]-5-fluoronicotinate수율 15%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

Ethyl 2-chloro-5-fluoro-nicotinate (J. Med. Chem. 1993, 36, 2676, M. Winn et. al.) (5.0 g, 24 mmol), 3-ethylsulfanylphenol (3.8 g, 24 mmol) and caesium carbonate (7.98 g, 24 mmol) were suspended in dioxan (50 ml) and the reaction was heated to 100° C. and stirred at this temperature under nitrogen for 8 h. The reaction was cooled to room temperature, filtered and the solid washed with ethyl acetate (50 ml). The filtrate was concentrated under reduced pressure, and the residue was purified by flash column chromatography on silica gel eluting with cyclohexane:ethyl acetate (95:5) to give 5-fluoro-2-(3-ethylsulfanyl-phenoxy)-nicotinic acid ethyl ester (1.16 g).

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered
  3. washthe solid washed with ethyl acetate (50 ml)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by flash column chromatography on silica gel eluting with cyclohexane:ethyl acetate (95:5)

출처 및 근거

ORD 기록
ord-2a1db452f43a4da3b881fa7b3b936d8a
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07141586B2

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