Hydrogen Peroxide → HCID 18796975、化合物

HRID 235066

反応式

HRID 235066 の反応式
[Cl:1][C:2]1[C:3]([C:8]#[N:9])=[N:4][CH:5]=[CH:6][CH:7]=1.OO.S([O-])([O-])=[O:13].[Na+].[Na+]>C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([C:8]#[N:9])=[N+:4]([O-:13])[CH:5]=[CH:6][CH:7]=1

参加物

6

反応物 3

HCID 784Hydrogen PeroxideHCID 24437Sodium SulfiteHCID 8182583-Chloropyridine-2-carbonitrile

生成物 1

HCID 18796975HCID 18796975、化合物収率 51.3%

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 962Water溶媒

反応条件

温度
90 °C

実験手順

To a solution of 3-chloro-2-cyanopyridine (40g, 0.29 mol) in 500 mL acetic acid added hydrogen peroxide (30%, 52 g, 0.45 mol) dropwise. After stirring at 90° C. for 18 h, the reaction is cooled to 25° C. and a solution of sodium sulfite (57 g, 0.45 mol) in H2O is added dropwise. The reaction is concentrated to remove the bulk of the acetic acid and the residue is partitioned between 1M NaOH and CH2Cl2. The CH2Cl2 layer is dried (MgSO4), filtered, concentrated, and recrystallized from EtOAc to provide 23 g (51%) of 3-chloro-2-cyanopyridine-N-oxide. The N-oxide from above (12.2 g, 79 mmol) was taken up in DMF (160 mL) at 0° C. Methyl thioglycolate (7.1 mL, 79 mmol) was added followed by sodium methoxide (8.5 g, 160 mmol) in portions. The RXN was stirred for 1 h. The RXN was poured onto ice and the resulting solid was collected by filtration, washed with water, dissolved in CH2Cl2, dried (MgSO4), filtered, concentrated, and recrystallized from EtOAc. 10.6 g (60%) of 3-amino-2-carbomethoxythieno[3,2-b]pyridine-4-oxide was obtained. The pyridine-N-oxide (10.6 g, 47 mmol) is mixed with phosphorous oxychloride (100 mL). The RXN is heated to 80° C. for 30 min. The RXN is concentrated and partitioned between CH2Cl2 and NaHCO3 sln. The CH2Cl2 layer is dried (MgSO4), filtered, cone, and chromatographed (5:1 hex:EtOAc). 8.3g (73%) of the 5-chloro and 2.0 g (18%) of the 7-chloro product were obtained: 1H NMR (300 MHz, CDCl3 (5-chloro)) δ3.92 (s, 3H), 6.15 (bs, 2H), 7.37 (d, 1H), 7.99 (d, 1H); MS (DCI/NH3) m/e 243 (M+H)+. 1H NMR (300 MHz, CDCl3 (7-chloro)) δ3.93 (s, 3H), 6.20 (bs, 2H), 7.41 (d, 1H), 8.54 (db, 1H); MS (DCI/NH3) m/e 243 (M+H)+.

後処理

  1. temperaturethe reaction is cooled to 25° C.
  2. concentrationThe reaction is concentrated
  3. customto remove the bulk of the acetic acid
  4. customthe residue is partitioned between 1M NaOH and CH2Cl2
  5. dry with materialThe CH2Cl2 layer is dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customrecrystallized from EtOAc

出典と根拠

ORDレコード
ord-13a18932739844ca964128d5d2968a2a
出典データセット
uspto-grants-1997_01
特許番号
US05597823

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