4-Methylquinoline → 2-(1-Fluorocyclopropyl)-4-(4-fluorophenyl)-4-methyl-1-quinolin-4-ylpentan-2-ol

HRID 400686ノート

反応式

HRID 400686 の反応式
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[Li].[F:13][C:14]1([C:17](=[O:29])[CH2:18][C:19]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)([CH3:21])[CH3:20])[CH2:16][CH2:15]1>C1COCC1>[F:13][C:14]1([C:17]([OH:29])([CH2:18][C:19]([C:22]2[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=2)([CH3:21])[CH3:20])[CH2:1][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][CH:3]=2)[CH2:15][CH2:16]1

参加物

5

反応物 3

HCID 102854-Methylquinoline2 回HCID 3028194LithiumHCID 600264051-(1-Fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-one

生成物 1

HCID 574481072-(1-Fluorocyclopropyl)-4-(4-fluorophenyl)-4-methyl-1-quinolin-4-ylpentan-2-ol収率 24.2%

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 4-methylquinoline (69 mg, 0.482 mmol) in THF cooled on dry ice/acetone was added 0.4 mL of lithium dilsopropylamide (1.5 M in hexanes). The mixture was placed in a cold bath at −20° C. to −30° C. for 15 minutes and then cooled to −78° C. 1-(1-Fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-one (49 mg, 0.206 mmol) was added dropwise as a solution in 0.5 mL of THF. The cold bath was then removed and the mixture stirred for 1 hour. The reaction was quenched by addition of 0.5 mL of water and diluted with ethyl acetate. The organic phase was separated, washed with water, dried, filtered, and the solvent evaporated in vacuo. Fractionation of the residue by preparative layer chromatography (developer: ethyl acetate-hexanes (2:1)) gave the title compound (0.019 g, 24% yield) (slightly less polar than lepidine) as an oil that crystallized on standing in hexanes, m.p. 152° C.-155° C.

後処理

  1. customThe cold bath was then removed
  2. customThe reaction was quenched by addition of 0.5 mL of water
  3. additiondiluted with ethyl acetate
  4. customThe organic phase was separated
  5. washwashed with water
  6. customdried
  7. filtrationfiltered
  8. customthe solvent evaporated in vacuo

出典と根拠

ORDレコード
ord-7f0814b7367e4ca19d7aeaa04d8b85f1
出典データセット
uspto-grants-2014_06
特許番号
US08741897B2

反応ノート

読み込み中…