Potassium Hydroxide → trans-2-Chloro-10,11-dihydro-11-[(methylamino)methyl]-dibenz[b,f]oxepin-10-carboxylic acid hydrochloride

The mixture of lactams (VII) and (VIII) (13.6 grams, 45 mmol, trans/cis ratio 1:2.3), obtained as described under E, was dissolved in ethanol (140 ml). To the solution potassium hydroxide was added (43 grams, 811 mmol), whereupon the mixture was heated to reflux for 18 hours. Part of the ethanol (60 ml) was evaporated and water was added (200 mL). The aqueous phase was extracted twice with toluene (100 ml). Subsequently toluene (100 ml) was added to the water phase, followed by concentrated hydrochloric acid to adjust the pH to 1. During the addition of hydrochloric acid the temperature rises to 75° C. The water layer was separated and upon cooling the product crystallized. The crystals were collected by filtration and dried to provide trans-2-chloro-10,11-dihydro-11-[(methylamino)methyl]-dibenz[b,f]oxepin-10-carboxylic acid hydrochloride (II) (3.75 grams, 10.6 mmol, 22%). M.p: 203.1° C. 1H-NMR (400 MHz, MeOD): 2.6 (s, 3H), 3.3 (s, 2H), 3.9 (m, 1H), 4.4 (d, 1H), 7.10-7.36 (m, 6H).

1. customobtained
2. temperaturewhereupon the mixture was heated
3. temperatureto reflux for 18 hours
4. customPart of the ethanol (60 ml) was evaporated
5. additionwater was added (200 mL)
6. extractionThe aqueous phase was extracted twice with toluene (100 ml)
7. additionSubsequently toluene (100 ml) was added to the water phase
8. additionDuring the addition of hydrochloric acid the temperature
9. customrises to 75° C
10. customThe water layer was separated
11. temperatureupon cooling the product
12. customcrystallized
13. filtrationThe crystals were collected by filtration
14. customdried

ORDレコード

ord-93c4a963f4cb44489f93ccee28df8973

出典データセット

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08426610B2