Pyridine → isobutyl 3-fluoro-4-(4-oxo-3,4-dihydropyridin-1(2H)-yl)phenylcarbamate

HRID 2213361ノート

反応式

HRID 2213361 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[C:4]([F:15])[CH:3]=1.N1C=CC=CC=1.Cl[C:23]([O:25][CH2:26][CH:27]([CH3:29])[CH3:28])=[O:24].C(OCC)(=O)C>ClCCl>[F:15][C:4]1[CH:3]=[C:2]([NH:1][C:23](=[O:24])[O:25][CH2:26][CH:27]([CH3:29])[CH3:28])[CH:7]=[CH:6][C:5]=1[N:8]1[CH:9]=[CH:10][C:11](=[O:14])[CH2:12][CH2:13]1

参加物

6

反応物 4

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 62365Isobutyl chloroformateHCID 218778771-(4-Amino-2-fluoro-phenyl)-2,3-dihydro-1H-pyridin-4-one

生成物 1

HCID 21957340isobutyl 3-fluoro-4-(4-oxo-3,4-dihydropyridin-1(2H)-yl)phenylcarbamate収率 72.6%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a cold (0° C.) stirring solution of the aniline from step 4 (62.0 g, 300.7 mmol) and pyridine (29.1 ml, 360.8 mmol) in dichloromethane (1095 ml) is added isobutyl chloroformate (42.9 ml, 330.7 mmol), and the mixture is stirred at ambient temperature for 90 min. Upon completion of the reaction the solvent is removed in vacuo, and the residual material is redissolved in dichloromethane (800 ml) and ethyl acetate (1100 ml). The mixture is washed with 10% aqueous HCl (1100 ml), and aqueous layer is extracted with 1:9/dichloromethane:ethyl acetate (1100 ml). The organic layers are combined and washed with brine (1100 ml). The organic layer is dried over MgSO4 and filtered. The filtrate is concentrated in vacuo. The residual material is recrystallized in 1:9/dichloromethane:ethyl acetate to afford 66.9 g (72% yield) of the title compound as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 0.93 (d, 6 H), 1.93 (m, 1 H), 2.47 (m, 2 H), 3.84 (m, 2 H), 3.89 (m, 2 H), 4.96 (d, 1 H) 7.29 (m, 2 H), 7.48 (m, 2 H), 9.92 (brs, 1 H).

後処理

  1. customUpon completion of the reaction the solvent
  2. customis removed in vacuo
  3. dissolutionthe residual material is redissolved in dichloromethane (800 ml)
  4. washThe mixture is washed with 10% aqueous HCl (1100 ml), and aqueous layer
  5. extractionis extracted with 1:9/dichloromethane
  6. washwashed with brine (1100 ml)
  7. dry with materialThe organic layer is dried over MgSO4
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated in vacuo
  10. customThe residual material is recrystallized in 1:9/dichloromethane

出典と根拠

ORDレコード
ord-b0d3d4d4115942e78e3aca0296b72382
出典データセット
uspto-grants-2006_09
特許番号
US07105547B2

反応ノート

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