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

HRID 870905노트

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HRID 870905 반응식
[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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9524dd65246f45778eea54fd1e0e2c8e
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969564B2

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