Diethyl Malonate → Diethyl (3-fluoro-2-pyridyl)malonate

HRID 523264노트

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HRID 523264 반응식
F[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[C:15]([O:23][CH2:24][CH3:25])(=[O:22])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]>CS(C)=O.CCOC(C)=O>[F:8][C:7]1[C:2]([CH:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:15]([O:23][CH2:24][CH3:25])=[O:22])=[N:3][CH:4]=[CH:5][CH:6]=1

참가 물질

6

반응물 3

HCID 7761Diethyl MalonateHCID 10796Cesium carbonateHCID 27831762,3-Difluoropyridine

생성물 1

HCID 57950221Diethyl (3-fluoro-2-pyridyl)malonate수율 60.3%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

A mixture of 2,3-difluoropyridine (2.00 g, 17.4 mmol), Cs2CO3 (13.59 g, 41.7 mmol) and diethyl malonate (6.68 g, 41.7 mmol) in DMSO (19 mL) was heated at 100° C. for 4.5 h. The mixture was poured onto ice, diluted with EtOAc, and the organic phase was separated, washed sequentially with water and brine, and dried and concentrated. The residue was purified by column chromatography on silica gel (80 g), eluting with EtOAc-hexanes (sequentially 10%, 20% and 30%), to provide diethyl 2-(3-fluoropyridin-2-yl)malonate as a pale colored oil (2.68 g, 60% yield). 1H NMR (400 MHz, chloroform-d) δ 8.42 (dt, J=4.6, 1.3 Hz, 1H), 7.43 (ddd, J=9.4, 8.3, 1.4 Hz, 1H), 7.30 (dt, J=8.5, 4.3 Hz, 1H), 5.09 (d, J=1.1 Hz, 1H), 4.30 (q, J=7.0 Hz, 4H), 1.33-1.26 (m, 6H).

후처리

  1. additionThe mixture was poured onto ice
  2. customthe organic phase was separated
  3. washwashed sequentially with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography on silica gel (80 g)
  7. washeluting with EtOAc-hexanes (sequentially 10%, 20% and 30%),

출처 및 근거

ORD 기록
ord-142b7053e592453ab1b6e8df89dd5274
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334290B2

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