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 1022604Notes

Reaction equation

HRID 1022604 reaction equation
[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]

Participants

8

Reactant 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, compound

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-9562f151821a41189674e76f724f7a05
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

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