反应详情

A suspension of 4-(4-chloro-phenyl)-4-[4-(3-methyl-1-trityl-1H-pyrazol-4-yl)-phenyl]-piperidine (178 mg, 0.30 mmol) in 5N hydrochloric acid (5 mL), THF (5 mL) and methanol (5 mL) was stirred for 140 minutes. The organic solvents were removed in vacuo then the resulting solution was diluted with 2N HCl and washed with ether. The aqueous phase was basified by addition of sodium hydroxide pellets then extracted with ethyl acetate. This organic extract was washed with brine, dried (MgSO4), filtered and concentrated to give a residue which was purified by column chromatography (SiO2), eluting with a gradient of 2M ammonia in methanol (5% to 7.5%) and dichloromethane. The product was further purified by preparative HPLC to give the title compound which was converted to its dihydrochloride salt (84 mg, 80%); LCMS (PS-A3) Rt 6.86 min [M+H]+ 352. 1H NMR (Me-d3-OD) δ 2.55 (3H, s), 2.70-2.75 (4H, m), 3.22-3.27 (4H, m), 7.35-7.41 (4H, m), 7.47-7.54 (4H, m), 8.32 (2H, s).

1. customThe organic solvents were removed in vacuo
2. additionthe resulting solution was diluted with 2N HCl
3. washwashed with ether
4. additionThe aqueous phase was basified by addition of sodium hydroxide pellets
5. extractionthen extracted with ethyl acetate
6. extractionThis organic extract
7. washwas washed with brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a residue which
12. customwas purified by column chromatography (SiO2)
13. washeluting with a gradient of 2M ammonia in methanol (5% to 7.5%) and dichloromethane
14. customThe product was further purified by preparative HPLC