1,2,3,4-Tetrahydro-benzo[b]azepin-5-one

Polyphosphoric acid (25g) was heated at 100°C under ni;trogen until it could be stirred. 1-(Toluene-4-sulfonyl)-1, 2, 3, 4-tetrahydro-benzo[b]azepin-5-one from Example E5.4 (2.6g, 8.2 6mmol) was added portionwise and the reaction mixture was heated at 100°C for 1.5h. It was poured into ice and basified with 2M NaOH(aq). The aqueous layer was extracted twice with dichloromethane. The organic extracts were combined, washed with brine, dried and reduced in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 40percent EtOAc: 60percent hexane) to yield the title compound (1.05g, 79percent).To a stirring solution of 1, 2, 3, 4-tertahydrobenzo[bjazepine-5-one (50 g, 0.31 mol) in DCM (250 mL) was added pyridine (175 mL). The mixture was cooled with ice bath and TsC1 (84 g, 0.44 mol) was added. The mixture was warmed to room temperature and stirredovernight. Water (750 mL) was added and the mixture was extracted with DCM (300 mL3). The combined organic phase was washed with water, brine, dried over anhydrous Na2504 and concentrated under reduced pressure. The residue was washed with a mixed solvent (petroleum ether/EtOAc = 70:1) to give the title product as a light yellowish solid (97 g, 99%). ESI MS m/z = 316.05 [M+HfTo a stirring solution of Step 1. Preparation of (+/-) 1- (Toluene-4-sulfonyl)-1, 2, 3, 4-tetrahydro-benzo [b] azepin-5- one. To a solution of 1, 2, 3, 4-Tetrahydro-benzo [b] azepin-5-one (500 mg, 3.1 mmol) in pyridine (2 ml) is added p-toluenesulfonyl chloride (650 mg, 3.4 mmol), and the mixture is heated at 50 C for 1 hour. The reaction mixture is poured into IN HCl (100 ml) and extracted with ethyl acetate (3x20 ml). The combined organic extracts are washed with brine, dried (Na2SO4), and concentrated to a solid. The solid is purified by silica gel column chromatography (eluent, 30 % ethyl acetate in hexanes) to give the title compound as a solid. Mass spectrum (ES+): 316 (M+H).Reference 1-tosyl-3, 4-Dihydro-1H-benzo[b]azepine-5(2H)-one (10.0g)Dissolved in pyridine (30 mL), Toluenesulfonium chloride (13.6 g) was added under ice bath, and stirred at room temperature for 12 hours. Water (60 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 40 minutes. The obtained crystals were collected by filtration, washed with water, and dried to give the title compound (18.9 g) as pale yellow white solid.

Molecular Weight:161.20
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:161.084063974
Monoisotopic Mass:161.084063974
Topological Polar Surface Area:29.1
Heavy Atom Count:12
Complexity:179
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes