Hydrochloric Acid → 1-Cyclobutyl-1,4-diazepane dihydrochloride

Temperature

55 °C

A 1-L, 3-necked, round-bottomed flask was equipped with a mechanical stirrer and a reflux condenser. The flask was charged with a slurry of crude 4-cyclobutyl-[1,4]diazepane-1-carboxylic acid tert-butyl ester (92.4 g, 363.8 mmol) in a mixture of dioxane/MeOH (100 mL/50 mL). HCl (4 M in dioxane, 250 mL) was added with vigorous mechanical agitation following which the reaction mixture was heated to ca. 55° C. in an oil bath. A pale orange-yellow solution resulted. The reaction mixture was maintained at ca. 55° C. for 16 h. After cooling to rt, the reaction mixture, a thick slurry, was transferred to a 2-L recovery flask and concentrated to a pasty solid. Methyl tert-butyl ether (200 mL) was added, and the slurry agitated at ca. 55° C. in an oil bath for 1 h. The solvent was removed by rotary evaporation under reduced pressure to afford the product as an off-white solid (81.2 g, 98%). 1H-NMR (400 MHz, DMSO-d6) δ ppm: 11.92 (s, 1H), 9.87 (s, 1H), 9.46 (s, 1H), 3.76-3.03 (m, 9H), 2.43-2.33 (m, 2H), 2.17-2.15 (m, 4H), 1.75-1.60 (m, 2H). MS m/z (ESI+): 155.1 (M+H+).

1. customA pale orange-yellow solution resulted
2. temperatureThe reaction mixture was maintained at ca. 55° C. for 16 h
3. temperatureAfter cooling to rt
4. customthe reaction mixture, a thick slurry, was transferred to a 2-L recovery flask
5. concentrationconcentrated to a pasty solid
6. additionMethyl tert-butyl ether (200 mL) was added
7. customThe solvent was removed by rotary evaporation under reduced pressure

ORD record

ord-56e9ab2184634cd4b46e92f9e5292685

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08940731B2