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

HRID 70674ノート

反応式

HRID 70674 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(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).

後処理

  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)

出典と根拠

ORDレコード
ord-a4584d7375584cad916d184117a0df8e
出典データセット
uspto-grants-2014_09
特許番号
US08822503B2

反応ノート

読み込み中…