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

HRID 475229ノート

反応式

HRID 475229 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-618a45e911274026b82c9329ef89eb81
出典データセット
uspto-grants-2014_01
特許番号
US08637537B2

反応ノート

読み込み中…