反应详情

(S)-2-methyl-propane-2-sulfinic acid {(S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butyl}-amide (38.83 g, 93.90 mmol) was dissolved in methanol and transferred to a 3-necked 1 L flask with overhead stirring and internal temperature. A total of 210 mL methanol was added to give a yellow solution. This was placed in an ice bath and at an internal temperature of 8° C., HCl in ether (188 mL, 2.0 M, 376 mmol) was added over 2 min. The temperature went up to 14° C. The ice bath was removed and the reaction stirred for ˜5 min as a yellow solution than as a white slurry. At 30 min, the reaction was rotovapped to dryness and the solid slurried in diethylether (200 mL) for 1 h. The solid was collected by Buchner filtration, washing with additional diethylether. This was suction dried for ˜1 h and then placed on the vacuum pump to give (S)-3-methyl-1-[2-(4-trifluoromethyl-phenyl)-pyrimidin-5-yl]-butylamine hydrochloride (31.58 g, 97%) as a white solid. 1H NMR (400 MHz, DMSO-d6, δ): 9.19 (s, 2H) 8.78 (br. s., 3H) 8.61 (d, J=8.2 Hz, 2H) 7.93 (d, J=8.4 Hz, 2H) 4.47 (br. s., 1H) 1.84-2.03 (m, 2H) 1.41 (m, 1H) 0.83-0.96 (m, 6H).

1. customtransferred to a 3-necked 1 L flask with overhead
2. customto give a yellow solution
3. additionwas added over 2 min
4. customwent up to 14° C
5. customThe ice bath was removed
6. stirringthe reaction stirred for ˜5 min as a yellow solution than as a white slurry
7. waitthe solid slurried in diethylether (200 mL) for 1 h
8. filtrationThe solid was collected by Buchner filtration
9. washwashing with additional diethylether
10. customThis was suction dried for ˜1 h