Hydrochloric Acid → HCID 86638055, compound

1,1-Dimethylethyl 7-(methyloxy)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate (15 mmol) was converted to 7-(methyloxy)-3-(trifluoroacetyl)-2,3,4,5-tetrahydro-1H-3-benzazepine as described in the initial steps of Preparation 23. This material (14 mmol) dissolved in dichloroethane (10 mL) was added at 0° C. to a previously prepared suspension of AlCl3 (4 eq) and propionyl chloride (1.3 eq) in dichloroethane (20 mL). The reaction mixture was stirred in a defrosting ice bath. After 4 h it had reached 12° C. when aqueous HCl (2 M, 40 mL) was carefully added over 20 min. Diethyl ether was added, layers separated and the organic layer washed with water and brine and dried over MgSO4. Volatiles were evaporated and the residue triturated with diethyl ether: cyclohexane 1:1 and then with diethyl ether to give a colourless powder (1-[8-hydroxy-3-(trifluoroacetyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-1-propanone, 1.2 g). To a solution of this material (0.43 g) in pyridine (2 mL) hydroxylamine hydrochloride (0.10 g) was added at room temperature and the reaction mixture was kept for 16 h. Additional hydroxylamine hydrochloride (0.03 g) was added. After 5 h the solvent was removed under vacuum, the residue treated with water (2 mL) and methanol (4 mL) with stirring until a solid started to form. Additional water (6 mL) was added. The resulting solid was collected by filtration, washed (water) and dried to give a white powder (0.39 g). This material (0.10 g) was dissolved in THF (1 ml) and Ph3P (0.13 g) was added. The reaction mixture was stirred at 50° C. while diisopropyl azodicarboxylate (94 μL) was added over 1 min, resulting in an orange solution. The reaction mixture was stirred at 50° C. for 15 min, then cooled to room temperature, and water (4 μL) was added. Solvent was removed under vacuum and the residue was submitted to column chromatography to provide the title compound (21 mg, colourless solid/film) of acceptable purity for further conversion.

1. customsteps of Preparation 23
2. customlayers separated
3. washthe organic layer washed with water and brine
4. dry with materialdried over MgSO4
5. customVolatiles were evaporated
6. customthe residue triturated with diethyl ether: cyclohexane 1:1

ORD record

ord-eb3f08031a784cfe8c7b93b14844c1a0

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989444B2