Trifluoroacetic acid → HCID 21473526, compound

1-(4-Hydroxy-2-methoxyphenyl)piperazine dihydrobromide (1.95 g, 5.27 mmol) was dissolved in 10 mL of THF and 10 mL of saturated sodium bicarbonate solution and then di(tert-butyl)pyrocarbonate (1.35 g, 6.2 mmol) was added. The mixture was stirred vigorously at room temperature for 18 hours and extracted with diethyl ether (3×25 mL). The combined extracts were washed with brine, dried (MgSO4) and filtered. The solvents were removed in vacuo and the residue was dissolved in 20 mL of DMF. The solution was treated with cesium carbonate (1.46 g, 4.5 mmol) and then benzyl bromide (1.1 g, 4.6 mmol) and stirred at room temperature under nitrogen for 3 hours. The mixture was partitioned between 50 mL of water and 50 mL of diethyl ether. The aqueous layer was separated and extracted with diethyl ether (2×50 mL). The combined diethyl ether was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified on silica gel by column chromatography eluting with hexanes/ethyl acetate (3:1) to give a pale yellow oil. The oil was dissolved in 20 mL of methylene chloride and the solution was treated with 10 mL of trifluoroacetic acid. After 45 minutes at room temperature the mixture was partitioned between 100 mL of 5M aqueous potassium carbonate and 100 mL of methylene chloride. The aqueous layer was separated and extracted with methylene chloride (2×100 mL). The combined methylene chloride was washed with brine, dried (Na2SO4), filtered and concentrated to give 1-(4-benzyloxy-2-methoxyphenyl)piperazine (1.39 g, 4.7 mmol).

1. extractionextracted with diethyl ether (3×25 mL)
2. washThe combined extracts were washed with brine
3. dry with materialdried (MgSO4)
4. filtrationfiltered
5. customThe solvents were removed in vacuo
6. dissolutionthe residue was dissolved in 20 mL of DMF
7. customThe mixture was partitioned between 50 mL of water and 50 mL of diethyl ether
8. customThe aqueous layer was separated
9. extractionextracted with diethyl ether (2×50 mL)
10. washThe combined diethyl ether was washed with brine
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue was purified on silica gel by column chromatography
15. washeluting with hexanes/ethyl acetate (3:1)
16. customto give a pale yellow oil
17. customAfter 45 minutes at room temperature the mixture was partitioned between 100 mL of 5M aqueous potassium carbonate and 100 mL of methylene chloride
18. customThe aqueous layer was separated
19. extractionextracted with methylene chloride (2×100 mL)
20. washThe combined methylene chloride was washed with brine
21. dry with materialdried (Na2SO4)
22. filtrationfiltered
23. concentrationconcentrated

ORD record

ord-c18d7f899ce144f6b6787e684f437c68

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05688795