Water → tert-butyl (6S,7R)-6-{[(3-cyanobenzyl)oxy]methyl}-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylate

HRID 1022681Notes

Reaction equation

HRID 1022681 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][C@H:10]2[CH2:23][OH:24])[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+].Br[CH2:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][CH:36]=1)[C:32]#[N:33].O>CN(C=O)C>[C:32]([C:31]1[CH:30]=[C:29]([CH:36]=[CH:35][CH:34]=1)[CH2:28][O:24][CH2:23][C@H:10]1[C@H:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:11]1)#[N:33]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 97249Benzonitrile, 3-(bromomethyl)-HCID 66975404tert-butyl (6S,7R)-7-(3,4-dichlorophenyl)-6-(hydroxymethyl)-1,4-oxazepane-4-carboxylate

Product 1

HCID 86663867tert-butyl (6S,7R)-6-{[(3-cyanobenzyl)oxy]methyl}-7-(3,4-dichlorophenyl)-1,4-oxazepane-4-carboxylateYield 85.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of tert-butyl (6S,7R)-7-(3,4-dichlorophenyl)-6-(hydroxymethyl)-1,4-oxazepane-4-carboxylate (144.5 mg) in DMF (3 mL) was added 60% sodium hydride (36.9 mg) at 0° C., and the mixture was stirred for 30 min. 3-(Bromomethyl)benzonitrile (90 mg) was added, and the mixture was warmed to room temperature and stirred overnight. The reaction mixture was poured into water, and the mixture was extracted twice with ethyl acetate. The organic layers were combined, and the mixture was washed with brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (162 mg).

Workup

  1. stirringstirred overnight
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. washthe mixture was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-68af5459530d42eab80d8843d82be005
Source dataset
uspto-grants-2014_05
Patent number
US08722662B2

Reaction notes

Loading…