反应详情

N-Boc-4-(4-chlorophenyl)-4-piperidine carboxylic acid Compound 2-1 (5.96 g, 18 mmol, Arch Chemical) was dissolved in DMF (175 mL) and chilled in an ice bath temp. To the solution was added N-methylmorpholine (5.76 mL, 53 mmol), HOBt (1.18 g, 8.8 mmol), dimethylamine hydrochloride (1.41 g, 18 mmol), and HBTU (10.0 g, 26 mmol). The solution was allowed to warm overnight to rt, poured into 1N sodium hydroxide solution (100 mL), and extracted with EtOAc (3×75 mL). The combined organic layers were washed with 1N NaOH (2×), 1N hydrochloric acid solution (2×), and brine (3×); and dried over Na2SO4 and concentrated to give Compound 2-2 (6.1 g, 17 mmol, 94%) as a white solid. 1H NMR (300 MHz, CDCl3,) δ 7.32 (d, J=9 Hz, 2H), 7.17 (d, J=9 Hz, 2H), 4.2-3.8 (br m, 2H), 3.0-2.6 (br m, 2H), 2.96 (s, 3H), 2.80 (s, 3H), 2.25 (m, 2H), 2.1-1.7 (br m, 2H), 1.45 (s, 9H).

1. temperaturechilled in an ice bath temp
2. temperatureto warm overnight to rt
3. extractionextracted with EtOAc (3×75 mL)
4. washThe combined organic layers were washed with 1N NaOH (2×), 1N hydrochloric acid solution (2×), and brine (3×)
5. dry with materialand dried over Na2SO4
6. concentrationconcentrated