Synthesis
General procedure for the synthesis of butoxycarbonyl-D-tyrosine-methoxylate from di-tert-butyl dicarbonate and (R)-2-amino-3-(4-hydroxyphenyl)propanoic acid methyl ester hydrochloride: potassium carbonate (250.9 g, 1.815 mol) was added to 1.0 L of water with stirring, and under ice-water-bath conditions, (R)-2-amino-3-(4-hydroxyphenyl)propanoic acid methyl ester hydrochloride ( 140.2 g, 0.605 mol), and then di-tert-butyl dicarbonate (158.4 g, 0.726 mol) was added slowly and dropwise. Ethanol (300 mL) was then added. After the dropwise addition, the reaction mixture was naturally warmed to room temperature and stirred for 2 h. The progress of the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, extraction was carried out with ethyl acetate (600 mL × 3), the organic phases were combined and washed sequentially with 1N hydrochloric acid (400 mL), water (400 mL) and saturated brine (400 mL × 2), and the organic phase was dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain a solid product, washed with 300 mL of hexane, and dried to give 175.8 g of white solid product in 98.4% yield.
References
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[4] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1997, vol. 36, # 7, p. 562 - 565
[5] Journal of Organic Chemistry, 1981, vol. 46, # 9, p. 1944 - 1946
