Radafaxine → Radafaxine Hydrochloride

Participants

Reaction Steps

1.26 g (0.005 mol) of optical isomer 2 (retention time 6.800 min) (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol) was dissolved in diethyl ether. The solution was filtered and the filtrate was chilled in an ice-bath adding ethereal hydrogen chloride until the solution was acidic. After standing at ambient temperature for 24 h, the resulting solid was filtered, washed with diethyl ether and dried in a vacuum oven at 60° C. for 18 h to give 1.36 g (93%) of (+)-(2S,3S)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride as a white solid: mp 208-209° C. NMR (300 Mhz, DMSO-d6); δ 9.87 (br, 1H), 8.76 (br, 1H), 7.54-7.41 (m, 5H), 3.99 (d, 1H), 3.51 (d, 1H), 3.37 (br s, 1H), 1.54 (s, 3H), 1.30 (s, 3H), 0.98 (d, 3H). Anal. Calcd for C13H19Cl2NO2: C, 53.43; H, 6.55; N, 4.79. Found: C, 53.51; H, 6.58; N, 4.73. ( α ) D 20 ⁢ ° ⁢   ⁢ C . = + 31.9 ⁢ ° ⁢   ⁢ ( 0.64 , 95 ⁢ % ⁢   ⁢ EtOH )

Provenance & Evidence