Hydrogen Peroxide → 3-chloro-2-cyanopyridine-N-oxide

HRID 442767노트

반응식

HRID 442767 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

HCID 187969753-chloro-2-cyanopyridine-N-oxide수율 51.3%

시약·촉매·용매 2

HCID 176Acetic Acid용매HCID 962Water용매

반응 조건

온도
90 °C

실험 절차

To a solution of 3-chloro-2-cyanopyridine (40 g, 0.29 mol) in 500 mL acetic acid was 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 was added dropwise. The reaction was concentrated to remove the bulk of the acetic acid and the residue is partitioned between 1M NaOH and CH2Cl2. The CH2Cl2 layer was dried (MgSO4), filtered, concentrated, and recrystallized from EtOAc to provide 23 g (51%) of 3-chloro-2-cyanopyridine-N-oxide. The resulting N-oxide (12.2 g, 79 mmol) was dissolved 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 reaction was stirred for 1 h. The reaction 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 methyl 3-amino-thieno[3,2-b]pyridine-4-oxide carboxylate was obtained. The pyridine-N-oxide (10.6 g, 47 mmol) was mixed with phosphorous oxychloride (100 mL). The reaction was heated to 80° C. for 30 min. The reaction was concentrated and partitioned between CH2Cl2 and 5% aq.NaHCO3 solution. The CH2Cl2 layer was dried (MgSO4), filtered, concentrated, and chromatographed (5:1 hex:EtOAc) to yield methyl 3-amino-5-chloro-thieno[3,2-b]pyridine-2-carboxylate (8.3 g, 73%): 1H NMR (300 MHz, CDCl3) d 3.92 (s, 3H), 6.15 (bs, 2H), 7.37 (d, 1H), 7.99 (d, 1H); MS (DCI/NH3) m/e 243 (M+H)+ ; followed by methyl 3-amino-7-chloro-thieno[3,2-b]pyridine-2-carboxylate (2.0 g, 18%): 1H NMR (300 MHz, CDCl3) d 3.93 (s, 3H), 6.20 (bs, 2H), 7.41 (d, 1H), 8.54 (db, 1H); MS (DCI/NH3) m/e 243 (M+H)+.

후처리

  1. temperaturethe reaction is cooled to 25° C.
  2. concentrationThe reaction was 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 was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customrecrystallized from EtOAc

출처 및 근거

ORD 기록
ord-8b9534493fe64e73b22876f1dd9931a5
출처 데이터셋
uspto-grants-1999_04
특허 번호
US05891882

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