Cyclobutanone → 5-{2-(4-Tert-butylphenyl)-2-[5-(1-hydroxycyclobutyl)-6-methoxypyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

HRID 70674노트

반응식

HRID 70674 반응식
Br[C:2]1[CH:3]=[CH:4][C:5](/[C:10](/[C:29]2[CH:34]=[CH:33][C:32]([C:35]([CH3:38])([CH3:37])[CH3:36])=[CH:31][CH:30]=2)=[CH:11]/[C@@H:12]2[N:16]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=3[O:26][CH3:27])[C:15](=[O:28])[CH2:14][CH2:13]2)=[N:6][C:7]=1[O:8][CH3:9].C([Li])CCC.[C:44]1(=[O:48])[CH2:47][CH2:46][CH2:45]1.[Cl-].[NH4+]>O1CCCC1>[C:35]([C:32]1[CH:31]=[CH:30][C:29]([C:10]([C:5]2[CH:4]=[CH:3][C:2]([C:44]3([OH:48])[CH2:47][CH2:46][CH2:45]3)=[C:7]([O:8][CH3:9])[N:6]=2)=[CH:11][CH:12]2[N:16]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=3[O:26][CH3:27])[C:15](=[O:28])[CH2:14][CH2:13]2)=[CH:34][CH:33]=1)([CH3:38])([CH3:36])[CH3:37]

참가 물질

6

반응물 4

HCID 14496CyclobutanoneHCID 25517Ammonium ChlorideHCID 67397955(5R)-5-[(E)-2-(5-bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-oneHCID 178418339Butyllithium

생성물 1

HCID 674003365-{2-(4-Tert-butylphenyl)-2-[5-(1-hydroxycyclobutyl)-6-methoxypyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

(5R)-5-[(E)-2-(5-Bromo-6-methoxypyridin-2-yl)-2-(4-tert-butylphenyl)ethenyl]-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one obtained in Reference Example 4-42(1) (100 mg) was dissolved in tetrahydrofuran (5 mL), and n-butyllithium was added at −78° C. After stirring for 30 minutes, cyclobutanone was added dropwise. The mixture was stirred for further 30 minutes and then an ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1) to give 5-{2-(4-tert-butylphenyl)-2-[5-(1-hydroxycyclobutyl)-6-methoxypyridin-2-yl]ethenyl}-1-(2,4-dimethoxybenzyl)pyrrolidin-2-one (EZ mixture) (35 mg).

후처리

  1. stirringThe mixture was stirred for further 30 minutes
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1→1:1)

출처 및 근거

ORD 기록
ord-a4584d7375584cad916d184117a0df8e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822503B2

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