Phosphorus oxychloride → 6-(4-Butoxyphenyl)-4-chloro-6-methyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile

HRID 1629802ノート

反応式

HRID 1629802 の反応式
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2([CH3:22])[NH:17][C:16](=[O:18])[C:15]([C:19]#[N:20])=[C:14](O)[CH2:13]2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].O=P(Cl)(Cl)[Cl:25].CCN(C(C)C)C(C)C>C(Cl)CCl>[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2([CH3:22])[NH:17][C:16](=[O:18])[C:15]([C:19]#[N:20])=[C:14]([Cl:25])[CH2:13]2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]

参加物

5

反応物 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 866858956-(4-Butoxyphenyl)-4-hydroxy-6-methyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile

生成物 1

HCID 866858966-(4-Butoxyphenyl)-4-chloro-6-methyl-2-oxo-1,2,5,6-tetrahydropyridine-3-carbonitrile収率 74%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

To a stirred solution of Intermediate 107E (130 mg, 0.433 mmol) in ClCH2CH2Cl (3 mL) was added POCl3 (0.056 mL, 0.606 mmol) and Hunig's base (0.113 mL, 0.649 mmol). The reaction was stirred at rt for 30 min and then heated to 85° C. for 3 h. The reaction mixture was concentrated and the residue was diluted with EtOAc. The organic layer was washed with saturated NH4Cl, dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes) to yield the desired product (102 mg, 74%) as a white solid. LCMS Anal. Calc'd for C17H19ClN2O2 318.11, found [M+H] 319.2. 1H NMR (500 MHz, CDCl3) δ 7.23 (d, J=8.80 Hz, 2H), 6.90 (d, J=8.80 Hz, 2H), 3.97 (t, J=6.60 Hz, 2H), 2.05 (s, 2H), 1.74-1.82 (m, 2H), 1.69 (s, 3H), 1.46-1.55 (m, 2H), 0.99 (t, J=7.43 Hz, 3H).

後処理

  1. temperatureheated to 85° C. for 3 h
  2. concentrationThe reaction mixture was concentrated
  3. additionthe residue was diluted with EtOAc
  4. washThe organic layer was washed with saturated NH4Cl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes)

出典と根拠

ORDレコード
ord-97f8a6af205c404a8dcb127c55fd066a
出典データセット
uspto-grants-2014_07
特許番号
US08791091B2

反応ノート

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