Sodium hydride → 8-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine

HRID 2369495ノート

反応式

HRID 2369495 の反応式
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][C:11]=2[CH:16]([CH:18]2[CH2:20][CH2:19]2)[OH:17])=[C:6](F)[CH:5]=1>C1COCC1>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]2[C:10]3[C:11](=[CH:12][N:13]=[CH:14][CH:15]=3)[CH:16]([CH:18]3[CH2:20][CH2:19]3)[O:17][C:6]=2[CH:5]=1

参加物

4

反応物 2

HCID 24758Sodium hydrideHCID 86695898(4-(4-Chloro-2-fluorophenyl)pyridin-3-yl)(cyclopropyl)methanol

生成物 1

HCID 866958998-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine収率 75.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a suspension of NaH (389 mg, 9.72 mmol) in THF (9 mL) cooled to 0° C., was added (4-(4-chloro-2-fluorophenyl)pyridin-3-yl)(cyclopropyl)methanol (900 mg, 3.24 mmol) in THF (9 mL) dropwise over a period of 10 min. The reaction mixture was stirred at 0° C. for 15 min and then warmed to room temperature and stirred for 15 h. The reaction mixture was quenched by addition of cold water (10 mL) and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with brine (1×25 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified via silica gel column chromatography (ethyl acetate/hexanes) to give 8-chloro-5-cyclopropyl-5H-chromeno[3,4-c]pyridine (630 mg, 2.45 mmol, 75% yield). LCMS (ESI) m/e 258.0 [(M+H)+, calcd for C15H13ClNO 258.1]; LC/MS retention time (Method C): tR=2.08 min.

後処理

  1. temperaturewarmed to room temperature
  2. stirringstirred for 15 h
  3. customThe reaction mixture was quenched by addition of cold water (10 mL)
  4. extractionextracted with ethyl acetate (3×25 mL)
  5. washThe combined organic extracts were washed with brine (1×25 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude residue was purified via silica gel column chromatography (ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-7e1a035927334e4387de5f541334e4dd
出典データセット
uspto-grants-2014_04
特許番号
US08703953B2

反応ノート

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