3-Bromophenol → HCID 13039279, compound

To a mixture of 4.78 g of cis-1-methyl-3-phenyl-4-piperidinol, 4.76 g of m-bromophenol, 7.21 g of triphenylphosphine and 125 ml of anhydrous benzene is added, dropwise at 5°-10° C. under nitrogen over a 45-minute period, a solution of 4.79 g of diethyl azodicarboxylate in benzene (100 ml). After the addition is complete the mixture is stirred overnight at room temperature, filtered and concentrated in vacuo. The residue is triturated overnight in a stoppered flask with hexane (250 ml). The hexane is decanted and the gummy solid triturated with 2:1/petroleum ether:ether solution to give a well-formed solid. The solid is washed with 2:1/petroleum ether:ether. The filtrates are combined and concentrated in vacuo to give a residue which is dissolved in ether (250 ml). The ether solution is extracted with 2 N hydrochloric acid (1×100 ml, 1×50 ml). The acid extracts are washed with ether (50 ml) and extracted with dichloromethane (1×100 ml, 1×50 ml). The dichloromethane extracts are washed with 10% aqueous sodium hydroxide solution (100 ml), water (100 ml), saturated sodium chloride solution (100 ml), dried overnight over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford an orange gum. Chromatography of the gum on 230 g of silica gel, using 25% methanol/acetone solution as solvent, gives a yellow gum. The latter is dissolved in ether (75 ml) and treated dropwise with a solution of 1.33 g of fumaric acid in a mixture of 30 ml of absolute ethanol and 105 ml of ether. After stirring overnight the mixture is filtered and the solid washed with ether and dried to afford a salt. Recrystallization from isopropanol (35 ml) affords product as a colorless, crystalline solid, mp 158.5°-160.5° C. dec.

1. additionis added, dropwise at 5°-10° C. under nitrogen over a 45-minute period
2. additionAfter the addition
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue is triturated overnight in a stoppered flask with hexane (250 ml)
6. customThe hexane is decanted
7. customthe gummy solid triturated with 2:1/petroleum ether
8. customether solution to give a well-formed solid
9. washThe solid is washed with 2:1/petroleum ether
10. concentrationconcentrated in vacuo
11. customto give a residue which
12. extractionThe ether solution is extracted with 2 N hydrochloric acid (1×100 ml, 1×50 ml)
13. washThe acid extracts are washed with ether (50 ml)
14. extractionextracted with dichloromethane (1×100 ml, 1×50 ml)
15. washThe dichloromethane extracts are washed with 10% aqueous sodium hydroxide solution (100 ml), water (100 ml), saturated sodium chloride solution (100 ml)
16. dry with materialdried overnight over anhydrous sodium sulfate
17. filtrationfiltered
18. concentrationconcentrated in vacuo
19. customto afford an orange gum
20. customgives a yellow gum
21. stirringAfter stirring overnight the mixture
22. filtrationis filtered
23. washthe solid washed with ether
24. customdried
25. customto afford a salt
26. customRecrystallization from isopropanol (35 ml)
27. customaffords product as a colorless, crystalline solid, mp 158.5°-160.5° C. dec.

ORD record

ord-63f2c6fb7ee748539c480876b6099d5a

Source dataset

uspto-grants-1983_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04382141