Hydrochloric Acid → HCID 53241830, compound

Temperature

100 °C

To Boc-anhydride (138 mg, 0.631 mmol) in dichloromethane (1 mL) was added DMAP (55.1 mg, 0.451 mmol) followed by a solution of 4-{[3-(methyloxy)phenyl]oxy}aniline (97 mg, 0.451 mmol) in dichloromethane (1 mL). The mixture was stirred for 10 min. The brown solution thus obtained was added to Solution 1 via syringe with shaking at 35° C. and shaking was continued at this temperature for 2 hours. The solution was then kept at room temperature for ca. 64 hours. Conc. aq. HCl (ca. 0.8 mL) was added and the heterogenous mixture was heated at 100° C. for 2 hours with shaking, allowing the DCM to distill off through a glass capillary. After cooling to room temperature, the residue was diluted with water (ca. 3 mL) and extracted with dichloromethane (2 times ca. 2 mL). The dichloromethane extracts were concentrated under vacuum. The residue was purified by silica gel chromatography (Biotage system, 10 g column) eluting with a gradient cHex/EtOAc from 95/5 to 0/100 to give a brown viscous oil that was dissolved in Et2O (ca. 0.7 mL) and cHex (ca. 0.1 mL) and kept over night. The overstanding faint brown solution was decanted from a small quantity of a brown oil that had separated out. As the solvent was allowed to evaporate from this solution crystallisation initiated. The material thus obtained was allowed to dry and then triturated with Et2O (2 times ca. 0.5 mL) to afford, after drying, the title compound as a solid (28 mg).

1. customThe brown solution thus obtained
2. stirringwith shaking at 35° C.
3. stirringshaking
4. waitwas continued at this temperature for 2 hours
5. waitThe solution was then kept at room temperature for ca. 64 hours
6. stirringwith shaking
7. distillationto distill off through a glass capillary
8. temperatureAfter cooling to room temperature
9. additionthe residue was diluted with water (ca. 3 mL)
10. extractionextracted with dichloromethane (2 times ca. 2 mL)
11. concentrationThe dichloromethane extracts were concentrated under vacuum
12. customThe residue was purified by silica gel chromatography (Biotage system, 10 g column)
13. washeluting with a gradient cHex/EtOAc from 95/5 to 0/100
14. customto give a brown viscous oil that
15. waitcHex (ca. 0.1 mL) and kept over night
16. customThe overstanding faint brown solution was decanted from a small quantity of a brown oil that
17. customhad separated out
18. customto evaporate from this solution crystallisation
19. customThe material thus obtained
20. customto dry
21. customtriturated with Et2O (2 times ca. 0.5 mL)
22. customto afford
23. customafter drying

ORD record

ord-b9641c97aedb4243879a1e3a315be28a

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216967B2