Synthesis
E) Preparation of N,N'-di-Boc-S-methylisothiourea: Di-tert-butyl dicarbonate (100 g, 458 mmol) was dissolved in tert-butanol (300 mL) under stirring conditions. Subsequently, a solution of S-methylisothiourea sulfate (32.7 g, 117 mmol) in water (150 mL) was slowly added, followed by dropwise addition of sodium hydroxide (19.2 g, 480 mmol) in water (150 mL). The reaction mixture was stirred continuously for 48 hours at room temperature. Upon completion of the reaction, the mixture was concentrated to one-third of the original volume under reduced pressure and then diluted with ether (500 mL). The organic phase was separated and washed once with water (250 mL), three times with 1N citric acid solution (250 mL), and again with water (250 mL), in that order. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 42 g (62% yield) of white solid product.
References
[1] Journal of Organic Chemistry, 1987, vol. 52, # 9, p. 1700 - 1703
[2] Patent: US5914319, 1999, A
[3] Patent: US5705487, 1998, A
[4] Patent: US5710130, 1998, A
[5] Patent: US5726159, 1998, A
