Sodium hydride → tert-butyl (6R,7R)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate

HRID 1022604노트

반응식

HRID 1022604 반응식
[H-].[Na+].[C:3]([C:5]1[C:6]([OH:11])=[N:7][CH:8]=[CH:9][CH:10]=1)#[N:4].[Br-].[Li+].[Cl:14][C:15]1[CH:16]=[C:17]([C@@H:22]2[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24][C@H:23]2[CH2:36]OS(C)(=O)=O)[CH:18]=[CH:19][C:20]=1[Cl:21]>COCCOC.O.CN(C=O)C>[C:3]([C:5]1[C:6](=[O:11])[N:7]([CH2:36][C@H:23]2[C@H:22]([C:17]3[CH:18]=[CH:19][C:20]([Cl:21])=[C:15]([Cl:14])[CH:16]=3)[O:28][CH2:27][CH2:26][N:25]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[CH2:24]2)[CH:8]=[CH:9][CH:10]=1)#[N:4]

참가 물질

8

반응물 4

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 86663851tert-butyl (6S,7R)-7-(3,4-dichlorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylateHCID 178510022HCID 178510022, 화합물

생성물 1

HCID 66975537tert-butyl (6R,7R)-6-[(3-cyano-2-oxopyridin-1(2H)-yl)methyl]-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate수율 86.2%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 80711,2-Dimethoxyethane용매2회

실험 절차

60% Sodium hydride (0.086 g) was added to a mixed solution of 3-cyano-2-hydroxypyridine (0.206 g) in 1,2-dimethoxyethane (4 ml)-DMF (2 ml) under ice-cooling, and the mixture was stirred for 5 min. To the reaction solution was added lithium bromide (0.248 g), and the mixture was stirred at room temperature for 0.5 hr. To the reaction solution was added a solution of tert-butyl (6S,7R)-7-(3,4-dichlorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylate (0.65 g) in 1,2-dimethoxyethane (4 mL), and the mixture was stirred at 60° C. overnight. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound (0.59 g, 86%).

후처리

  1. temperaturecooling
  2. stirringthe mixture was stirred at room temperature for 0.5 hr
  3. stirringthe mixture was stirred at 60° C. overnight
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-9562f151821a41189674e76f724f7a05
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08722662B2

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