反应详情

温度

55 °C

(R)-2-(3-Chlorophenyl)-morpholine-4-carboxylic acid tert-butyl ester was prepared using a similar procedure as that described in Example 4 (steps b-d). (R)-2-(3-Chloro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (2.7 g, 9.07 mmol) was dissolved in HCl in dioxane (4M, 11.3 mL, 45.3 mmol) and the resulting mixture was heated at 55° C. for 2 h and then stirred at room temperature overnight. The solvent was removed by concentration in vacuo. The crude product was purified by reverse phase column chromatography (5-80% acetonitrile containing 0.1% TFA in water containing 0.1% TFA). The desired fractions were pooled and concentrated in vacuo. The product was dissolved in acetonitrile and water and 0.1 mL of concentrated HCl was added. The resultant solution was lyophilized to afford (R)-2-(3-chlorophenyl)-morpholine hydrochloride (0.71 g), as a white solid. 1H NMR (400 MHz, DEUTERIUM OXIDE) δ ppm 3.18 (dd, J=12.80, 11.54 Hz, 1H) 3.30 (dd, J=12.17, 3.89 Hz, 1H) 3.34-3.51 (m, 2H) 3.99 (ddd, J=13.11, 12.11, 2.64 Hz, 1H) 4.22 (dd, J=13.18, 3.64 Hz, 1H) 4.82 (dd, J=11.42, 2.38 Hz, 1H) 7.26-7.33 (m, 1H) 7.34-7.42 (m, 2H) 7.44 (d, J=1.76 Hz, 1H).

1. customThe solvent was removed by concentration in vacuo
2. customThe crude product was purified by reverse phase column chromatography (5-80% acetonitrile containing 0.1% TFA in water containing 0.1% TFA)
3. concentrationconcentrated in vacuo
4. dissolutionThe product was dissolved in acetonitrile
5. additionwater and 0.1 mL of concentrated HCl was added