Sodium hydride → 3-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4-bromo-benzoic acid ethyl ester

HRID 1920007Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

4-Bromo-3-bromomethyl-benzoic acid ethyl ester (2.95 g, 9.2 mmol) and ethyl-carbamic acid benzyl ester (3.30 g, 18.4 mmol) were combined in DMF (100 mL) and cooled to 0° C. Sodium hydride (60% in mineral oil; 0.772 g, 19.3 mmol) was added slowly, and the reaction was stirred at room temperature for 10 minutes. The mixture was quenched with H2O and 1N aqueous HCl (20 mL), and then extracted with 1:1 EtOAc:hexanes three times. The organic layer was washed with brine, and then dried and concentrated. The residue was purified by silica gel chromatography (0-100% EtOAc in hexanes) to give the title compound, as well as the hydrolyzed product, which was combined with the product from the next step.

Workup

customThe mixture was quenched with H2O and 1N aqueous HCl (20 mL)
extractionextracted with 1:1 EtOAc
washThe organic layer was washed with brine
customdried
concentrationconcentrated
customThe residue was purified by silica gel chromatography (0-100% EtOAc in hexanes)

Sources & evidence

ORD record: ord-f494438aafe844f696e02afeb958732a
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168678B2

Reaction notes

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