Sodium hydride → tert-Butyl (3R,7R)-1-(cyclopropylmethyl)-2-oxo-7-phenylazepan-3-ylcarbamate

HRID 1271472Notes

Reaction equation

HRID 1271472 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C@H:10]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:9][CH2:8][CH2:7][C@H:6]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[NH:5]1.[CH:25]1([CH2:28]Br)[CH2:27][CH2:26]1>CN(C)C=O>[CH:25]1([CH2:28][N:5]2[C@@H:6]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH2:7][CH2:8][CH2:9][C@@H:10]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[C:4]2=[O:3])[CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 86607389tert-Butyl (3R,7R)-2-oxo-7-phenylazepan-3-ylcarbamate

Product 1

HCID 86607390tert-Butyl (3R,7R)-1-(cyclopropylmethyl)-2-oxo-7-phenylazepan-3-ylcarbamateYield 69.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil; 14.4 mg, 0.36 mmol) was added to a solution of tert-butyl (3R,7R)-2-oxo-7-phenylazepan-3-ylcarbamate (100 mg, 0.33 mmol) and cyclopropylmethyl bromide (0.08 mL, 0.82 mmol) in N,N-dimethylformamide (1 mL) at 0° C., and the mixture was allowed to warm to ambient temperature. After 6 h, the reaction was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with water (3×), saturated brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (10% ethyl acetate/hexanes→50% ethyl acetate/hexanes) gave the title compound (82 mg). MS 359 (M+1).

Workup

  1. customthe reaction was quenched with water
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with water (3×), saturated brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (10% ethyl acetate/hexanes→50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c3c858aa4829418f8c44f61ba510823d
Source dataset
uspto-grants-2007_04
Patent number
US07205292B2

Reaction notes

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