Hydrochloric Acid → 6-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine hydrochloride

Dissolve crude 6-methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (35.1 g, 0.198 mol) in 2B-3 ethanol (250 mL), heat the solution to reflux and add 2M HCl in ethanol (108.9 mL, 0.218 mol, 1.1 equiv.). Slowly add heptane (700 mL) over 10 min, then remove the heating mantle and cool the solution to ambient temperature, and finally continue the cooling with an ice/water mixture. Collect the resulting solid by vacuum filtration and wash with cold ethanol:heptane (1:2) (3×100 mL), air-dry for 15 min under vacuum, then further dry the product in a vacuum oven at 60° C. for 1 h to give the desired intermediate as a white granular solid (35.53 g, 63%): mp 246.6-246.9° C.; 1H NMR (300 MHz, DMSO-d6), δ 9.82 (broad s, 1H), 7.12 (dd, 1H, J=7.6, 7.9), 6.88 (d, 1H J=8.2), 6.78 (d, 1H, J=7.3), 3.75 (s, 3H), 3.20-3.00 (m, 8H); 13C NMR (300 MHz, DMSO-d6), δ 156.2, 141.3, 127.4, 127.2, 121.6, 109.7, 55.7, 44.9, 44.7, 31.6, 21.7; MS (ES+) m/z 178 (M+H)+; Anal. Calc'd for C11H15ClNO: C, 62.12; H, 7.11; N, 6.59. Found: C, 61.95, H, 7.64; N, 6.58.

1. temperatureheat the solution
2. temperatureto reflux
3. customremove the heating mantle
4. customCollect the resulting solid
5. filtrationby vacuum filtration
6. washwash with cold ethanol:heptane (1:2) (3×100 mL)
7. customair-dry for 15 min under vacuum
8. customfurther dry the product in a vacuum oven at 60° C. for 1 h

ORD record

ord-e284ef41a8cc40ffaee8274b3c70333f

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680091B2