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

HRID 523264ノート

反応式

HRID 523264 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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%),

出典と根拠

ORDレコード
ord-142b7053e592453ab1b6e8df89dd5274
出典データセット
uspto-grants-2016_05
特許番号
US09334290B2

反応ノート

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