Synthesis
Example 2: General procedure for the synthesis of 2-chloro-N-methylethylamine hydrochloride from N-methyl-2-hydroxyethylamine
1. Dry hydrogen chloride gas was passed into a solution of dichloromethane (25 ml) containing 2-(methylamino)ethanol (10 g, 133 mmol) under stirring conditions until the mixture turned wet litmus paper red.
2. The reaction mixture was cooled to 0 °C and thionyl chloride (15.82 g, 133 mmol) was added slowly and dropwise.
3. After the dropwise addition was completed, the reaction mixture was stirred at room temperature overnight.
4. After completion of the reaction, the solvent was removed by distillation under reduced pressure to afford the target product 2-chloro-N-methylethylamine hydrochloride as a white solid (16.60 g, 96% yield).
Product characterization: melting point 95°-100°C; 1H NMR (DMSO-d6) δ 4.00 (t, 2H, J = 6.28Hz), 3.36 (t, 2H, J = 6.29Hz), 2.81 (s, 3H); IR (KBr) ν 3400, 2960, 2750, 2420, 1730, 1580, 1460, 1390, 1310, 1270, 1200, 1310, 1270, 1200, 1390, 1390. 1310, 1270, 1200, 1150, 1165, 1005, 990, 900, 860, 710 cm-1.
References
[1] Journal of Medicinal Chemistry, 1995, vol. 38, # 14, p. 2672 - 2680
[2] Patent: US5233031, 1993, A
[3] Chemical and Pharmaceutical Bulletin, 2002, vol. 50, # 7, p. 941 - 959
[4] Journal of the Chemical Society. Dalton Transactions, 2001, # 8, p. 1306 - 1318
[5] Journal of medicinal chemistry, 1992, vol. 35, # 17, p. 3246 - 3253
