反应详情

A solution of 4-[2-(4-chlorophenoxy)phenylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester (AMR01031, 410 mg, 0.95 mmol) in 4M HCl in dioxane (2 mL) was stirred at room temperature for 2 h. The resulting solution was concentrated under vacuum and the residue was dissolved in DCM, washed with 1M NaOH (1×20 mL), water and brine. The organic layer was dried (MgSO4), filtered and evaporated to give piperidine-4-carboxylic acid [2-(4-chlorophenoxy)phenyl]amide (233 mg, 74%) as a white solid (mp 138-140° C. from hexane/EtOAc), which was used in the next step without further purification. Rf: 0.11 (DCM/methanol 4:1 plus 3 drops of triethylamine) 1H NMR (270 MHz, CDCl3) δ 1.62 (2H, m, CH2), 1.83 (3H, m, CH2+NH), 2.35 (1H, tt, J=11.6, 3.7 Hz, CH), 2.62 (2H, br t, CH2), 3.20 (2H, br d, J=12.3 Hz, CH2), 6.80 (1H, td, ArH), 6.92 (2H, AA′BB′, ArH), 6.98 (1H, td, ArH), 7.11 (1H, td, ArH), 7.29 (1H, AA′BB′, ArH), 7.71 (1H, br s, NHCO) and 8.41 (1H, br d, J=7.9 Hz, ArH).

1. concentrationThe resulting solution was concentrated under vacuum
2. dissolutionthe residue was dissolved in DCM
3. washwashed with 1M NaOH (1×20 mL), water and brine
4. dry with materialThe organic layer was dried (MgSO4)
5. filtrationfiltered
6. customevaporated