6-BROMO-3,4-DIHYDRO-4,4-DIMETHYLQUINOLIN-2(1H)-ONE

General procedure: To a solution of 4-bromoaniline (5.0 g, 29.1 mmol) in DCM (100 mL) was added 3, 3-dimethylacryloyl chloride (3.40 mL, 30.6 mmol) and the resultant white suspension was stirred for 0.5 h, after which pyridine (9.70 mL, 30.6 mmol) was added and the solution stirred at rt for 16 h. The solution was diluted with DCM and H2O, washed with sat. NH4Cl, H2O, dried (MgSO4) and evaporated to give a crude light brown solid (33 g) which was recrystallised from hexane to give N-(4-bromophenyl)-3-methylbut-2-enamide as a white solid (6.87 g, 94percent). N-(4-Bromophenyl)-3-methylbut-2-enamide (4.5 g, 17.7 mmol) and AlCl3 (3.54 g, 26.6 mmol) were added to anhydrous DCM (90 mL) under Ar and the resultant solution stirred vigorously for 2.5 h at rt. The reaction was then cooled to 0 °C, quenched slowly with H2O, diluted with DCM, stirred with 20percent NaOH (w/v) until the solution turned off-white, then further washed with H2O, dried (MgSO4) and evaporated to give 6-bromo-4, 4-dimethyl-1, 2, 3, 4-tetrahydroquinolin-2-one (4.07 g, 90percent). To a solution of 6-bromo-4, 4-dimethyl-1, 2, 3, 4-tetrahydroquinolin-2-one (4.07 g, 16.02 mmol) in anhydrous DMF (50 mL) was added crushed KOH (2.70 g, 48.06 mmol) and the resultant slurry stirred for 1 h at 50 °C under Ar. To this was added 2-iodopropane (4.8 mL, 48.06 mmol) and the solution stirred at 50 °C for 40 h. The reaction was quenched with H2O, diluted with EtOAc, washed with sat. NH4Cl, H2O and brine, dried (MgSO4) and evaporated to give a crude clear oil. This was purified by SiO2 chromatography (hexane/EtOAc 9:1, with 1percent Et3N as eluent) to give 6-bromo-4, 4-dimethyl-1-(propan-2-yl)-1, 2, 3, 4-tetrahydroquinolin-2-one as a colourless oil (2.19 g, 46percent):1H NMR (700 MHz; CDCl3) δ 1.27 (s, 6H), 1.51 (d, J = 7.0 Hz, 6H), 2.40 (s, 2H), 4.68 (sept, J = 7.1 Hz, 1H), 7.00 (d, J = 8.7 Hz, 1H), 7.32 (dd, J = 8.7, 2.3 Hz, 1H), 7.36 (d, J = 2.3 Hz, 1H); 13C NMR (176 MHz; CDCl3) δ 20.4, 26.8, 33.2, 47.2, 48.9, 116.4, 118.6, 127.6, 129.9, 138.6, 138.9, 169.8; IR (neat) max/cm–12964m, 2934w, 2872w, 1671s, 1590m, 1484s, 1417m, 1332s, 1253s, 811s; MS (ES): m/z = 296.4 [M+H]+; HRMS (ES) calcd. for C14H19NOBr [M+H]+: 296.0650, found: 296.0658.Aluminum chloride (5 g, 37.5 mmol) was added portionwise to N-(4-bromophenyl)-3-methylbut-2-enoic amide (Compound 26, 7.69 g, 30.0 mmol) in a 500 mL beaker at 130° C. over 1 h. The beaker was then cooled to 80° C. and another portion of aluminum chloride (1 g, 7.5 mmol) was added. After stirring at 80° C. for 0.5 h, the beaker was cooled with an ice-bath and ice was added slowly into the mixture. The resulting slurry was then extracted with ether (3*10 mL). The combined organic layer was washed with brine (1*10 mL), saturated NaHCO6-Bromo-4, 4-dimethyl-3, 4-dihydro-1H-quinolin-2-one (Intermediate 4)

Molecular Weight:254.12
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:253.01023
Monoisotopic Mass:253.01023
Topological Polar Surface Area:29.1
Heavy Atom Count:14
Complexity:252
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes