2-Bromoaniline → 5-(2-bromo-phenylcarbamoyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 83981

Reaction equation

C[Al](C)C.[Br:5][C:6]1[CH:12]=[CH:11][CH:10]=[CH:9][C:7]=1[NH2:8].C[O:14][C:15]([C:17]1[CH2:18][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20][CH2:21][CH:22]=1)=O>ClCCl>[C:26]([O:25][C:23]([N:19]1[CH2:18][C:17]([C:15](=[O:14])[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[Br:5])=[CH:22][CH2:21][CH2:20]1)=[O:24])([CH3:29])([CH3:28])[CH3:27]

Participants

Conditions

Temperature: 0 °C

Procedure

Trimethylaluminium (2M in heptane, 3 ml) was added dropwise to a solution of 2-bromoaniline (860 mg) in dichloromethane (15 ml). After gas evolution ceased, 5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (Chem. Commun. 1999, 1757-1758, 1.2 g) dissolved in dichloromethane (10 ml) was added and the resulting mixture was refluxed for 5 hrs. The solution was cooled to 0° C., quenched by careful addition of saturated aqueous sodium bicarbonate (10 ml) and extracted with dichloromethane. The organic layer was washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (eluent cyclohexane:ethyl acetate 85:15) to afford 5-(2-bromo-phenylcarbamoyl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (1.2 g), which was characterised by its mass and NMR spectra.

Workup

additionwas added
temperaturethe resulting mixture was refluxed for 5 hrs
customquenched by careful addition of saturated aqueous sodium bicarbonate (10 ml)
extractionextracted with dichloromethane
washThe organic layer was washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography (eluent cyclohexane:ethyl acetate 85:15)

Sources & evidence

ORD record: ord-ef6ef8d06845496a96b911312e08976f
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846907B2

Linked notes

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