Sodium hydride → tert-Butyl (3R)-1-(cyclopropylmethyl)-2-oxoazepan-3-ylcarbamate

HRID 1725615Notes

Reaction equation

HRID 1725615 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][CH2:6][NH:5]1.[CH:19]1([CH2:22]Br)[CH2:21][CH2:20]1>CN(C)C=O>[CH:19]1([CH2:22][N:5]2[CH2:6][CH2:7][CH2:8][CH2:9][C@@H:10]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16])[C:4]2=[O:3])[CH2:21][CH2:20]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 2756761(R)-tert-Butyl (2-oxoazepan-3-yl)carbamate

Product 1

HCID 58695830tert-Butyl (3R)-1-(cyclopropylmethyl)-2-oxoazepan-3-ylcarbamateYield 80.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil; 30 mg, 1.24 mmol) was added to a solution tert-butyl (3R)-2-oxoazepan-3-ylcarbamate (258 mg, 1.13 mmol) and cyclopropylmethyl bromide (0.27 mL, 2.83 mmol) in N,N-dimethylformamide (3 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 (100% dichloromethane→5% methanol/dichloromethane) gave the title compound (257 mg). MS 283 (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 (100% dichloromethane→5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-7c5f8a97779e464d9e6944b56ba50660
Source dataset
uspto-grants-2009_02
Patent number
US07491713B2

Reaction notes

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