Hydrochloric Acid → HCID 21070815, compound

Degassed ethyl acetate (75 ml) was added to 5.5 g (19.6 mmol) 2-(ethyl)(2-hydroxyphenyl)aminoethylcarbamic acid, 1,1-dimethylethyl ester (6). To this was added 50 ml of 3N HCl and the reaction was stirred at ambient temperature overnight. TLC analysis was done using 30% EtOAc/hexanes. The reaction mixture was tranferred to a separatory funnel and extracted with 2×40 ml 1N HCl. The pooled aqueous layers were placed on the rotary evaporator and the volatiles removed. Water was added (about 50 ml) and removed by rotary evaporation, 2 cycles. The resulting oil was frozen in dry ice and placed under vacuum, then allowed to warm naturally to remove all volatiles. The resulting crispy material (7) was used without further purification, and kept free of air and moisture. Dry pyridine (75 ml) was added to the isolate by cannula. The flask was swirled to dissolve the material. Acetic anhydride (1.2 eq.) was added via syringe and the reaction was stirred under argon at ambient temperature. TLC analysis was performed with 10% methanol/chloroform. At the completion of the reaction, the pyridine was removed by rotary evaporation and the residue treated with 100 ml of 10% NaOH by stirring overnight under argon. The reaction was adjusted to pH 9 with 1N HCl and extracted with 4×75 ml ethyl acetate. The combined organic layers were washed with water, then brine (once each), pre-dried with Na2SO4, then dried overnight with MgSO4. The solution was collected by filtration and the volatiles were removed by rotary evaporation. The material was purified by flash chromatography on silica: loaded with 5% methanol/chloroform; eluted with 150 ml each of 3.3, 6.6, and 9.9% solvent as above to give 3-(ethyl)(2-acetylaminoethyl)aminophenol (8). Yield was 4.2 g (96%).

1. customDegassed ethyl acetate (75 ml)
2. customThe reaction mixture was tranferred to a separatory funnel
3. extractionextracted with 2×40 ml 1N HCl
4. customThe pooled aqueous layers were placed on the rotary evaporator
5. customthe volatiles removed
6. additionWater was added (about 50 ml)
7. customremoved by rotary evaporation, 2 cycles
8. temperatureThe resulting oil was frozen in dry ice
9. temperatureto warm naturally
10. customto remove all volatiles
11. customThe resulting crispy material (7) was used without further purification
12. additionDry pyridine (75 ml) was added to the
13. customisolate by cannula
14. dissolutionto dissolve the material
15. stirringthe reaction was stirred under argon at ambient temperature
16. customAt the completion of the reaction
17. customthe pyridine was removed by rotary evaporation
18. additionthe residue treated with 100 ml of 10% NaOH
19. stirringby stirring overnight under argon
20. extractionextracted with 4×75 ml ethyl acetate
21. washThe combined organic layers were washed with water
22. dry with materialbrine (once each), pre-dried with Na2SO4
23. dry with materialdried overnight with MgSO4
24. filtrationThe solution was collected by filtration
25. customthe volatiles were removed by rotary evaporation
26. customThe material was purified by flash chromatography on silica
27. washeluted with 150 ml each of 3.3, 6.6, and 9.9% solvent as above

ORD record

ord-b86647adf94a47f287e9c2b6f85bf1a5

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07449315B2