Dimethylformamide → 4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde

HRID 475229노트

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HRID 475229 반응식
Br[C:2]1[CH:16]=[CH:15][C:5]2[N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[CH:7]=[N:8][C:4]=2[C:3]=1[F:17].CCCCCC.CN([CH:27]=[O:28])C>C1COCC1>[F:17][C:3]1[C:4]2[N:8]=[CH:7][N:6]([CH:9]3[CH2:14][CH2:13][CH2:12][CH2:11][O:10]3)[C:5]=2[CH:15]=[CH:16][C:2]=1[CH:27]=[O:28]

참가 물질

5

반응물 3

HCID 6228DimethylformamideHCID 8058HexaneHCID 866947315-bromo-4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole

생성물 1

HCID 866947324-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde수율 93%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a solution of 146 (10 g, 0.034 mol) in dry THF (100 mL) at −78° C. was added dropwise 1.6 M N-butyl lithium solution in hexane (23 mL, 0.0374 mol). After stirring for 45 min at −78° C., a solution of DMF (5 g, 0.068 mol) in THF (20 mL) was added dropwise. After 1 h at −78° C. the reaction mixture was quenched slowly by adding water. The aqueous phase separated was extracted with EtOAc and the combined organic extracts washed with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with 15% EtOAc/petroleum ether to afford 7.7 g (93%) of 4-fluoro-1-(tetrahydro-pyran-2-yl)-1H-benzoimidazole-5-carbaldehyde (148) as a yellow solid.

후처리

  1. customAfter 1 h at −78° C. the reaction mixture was quenched slowly
  2. additionby adding water
  3. customThe aqueous phase separated
  4. extractionwas extracted with EtOAc
  5. washthe combined organic extracts washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by SiO2 chromatography
  10. washeluting with 15% EtOAc/petroleum ether

출처 및 근거

ORD 기록
ord-618a45e911274026b82c9329ef89eb81
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637537B2

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