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

HRID 400686노트

반응식

HRID 400686 반응식
[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

참가 물질

5

반응물 3

HCID 102854-Methylquinoline2회HCID 3028194LithiumHCID 600264051-(1-Fluorocyclopropyl)-3-(4-fluorophenyl)-3-methylbutan-1-one

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-7f0814b7367e4ca19d7aeaa04d8b85f1
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741897B2

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