Phosphorus oxychloride → HCID 71743978、化合物

HRID 245848ノート

反応式

HRID 245848 の反応式
P(Cl)(Cl)(Cl)=O.[F:6][C:7]1[C:8]([CH2:14][NH:15][CH:16]=O)=[N:9][CH:10]=[C:11]([F:13])[CH:12]=1>C1(C)C=CC=CC=1>[F:13][C:11]1[CH:12]=[C:7]([F:6])[C:8]2[N:9]([CH:16]=[N:15][CH:14]=2)[CH:10]=1

参加物

4

反応物 2

HCID 24813Phosphorus oxychlorideHCID 86677903N-[(3,5-Difluoro-2-pyridinyl)methyl]formamide

生成物 1

HCID 71743978HCID 71743978、化合物収率 45%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

In a round-bottomed flask, N-(3,5-difluoro-pyridin-2-ylmethyl)-formamide (crude from Step 2) was dissolved in toluene (14 ml) and phosphorus oxychloride (0.65 ml, 7.0 mmol) was added. The reaction mixture was stirred at 100° C. in an oil bath for 3.5 h then cooled to 0° C. and carefully quenched with ice. Aqueous 25% ammonium hydroxide was added until pH=˜9. The mixture was diluted with water and extracted with dichloromethane (3×). The organic layers were combined, dried over sodium sulfate, filtered and concentrated. The residue was absorbed on silica gel and chromatographed with EtOAc/hexanes (gradient 0-60% EtOAc) to give 319 mg (45%, 2 steps) of 6,8-difluoro-imidazo[1,5-a]pyridine as a yellow solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.36 (d, J=3.0 Hz, 1H), 7.84 (d, J=3.4 Hz, 1H), 7.65 (s, 1H), 6.39-6.57 (m, 1H).

後処理

  1. temperaturethen cooled to 0° C.
  2. customcarefully quenched with ice
  3. additionAqueous 25% ammonium hydroxide was added until pH=˜9
  4. additionThe mixture was diluted with water
  5. extractionextracted with dichloromethane (3×)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was absorbed on silica gel
  10. customchromatographed with EtOAc/hexanes (gradient 0-60% EtOAc)

出典と根拠

ORDレコード
ord-cdd3b90958f943829d297eba0db7fa78
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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