Uses
N-Boc-D-tert-leucine is a protected form of D-tert-leucine, and is used in the synthesis of primary amino acid derivatives (e.g. Desacetyl Desmethyl Lacosamide [D288325]) that possess anticonvulsant and neuropathic pain protection properties.
Synthesis
General procedure for the synthesis of tert-butoxycarbonyl-D-tert-leucine from D-tert-leucine and di-tert-butyl dicarbonate: 3-methyl-D-valine (900 mg, 6.86 mmol) was dissolved in a mixture of 7 mL of a 1 M aqueous sodium hydroxide solution and 7 mL of methanol at 0°C, followed by the addition of di-tert-butyl dicarbonate (Boc-anhydride, 1.797 g, 8.23 mmol). The reaction mixture was gradually warmed to room temperature and stirred continuously overnight. Upon completion of the reaction, most of the methanol was removed by evaporation, and the reaction solution was acidified to pH 2 with 1 M aqueous HCl, followed by three extractions with ethyl acetate (3 × 20 mL). The organic phases were combined and washed twice with brine (2 × 5 mL). Finally, the solvent was removed by evaporation to afford tert-butoxycarbonyl-D-tert-leucine as a white solid in 83% yield (1.36 g). The product was characterized by NMR (400 MHz, DMSO-d6): δ 12.44 (1H, s), 6.82 (1H, d), 3.76 (1H, d), 1.38 (9H, s); UPLC analysis showed a retention time of 0.64 min and a molecular ion peak of 232 [M + H]+.
References
[1] Patent: WO2011/69951, 2011, A1. Location in patent: Page/Page column 77
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 15, p. 4620 - 4631
[3] Journal of Medicinal Chemistry, 2011, vol. 54, # 13, p. 4815 - 4830
[4] Patent: WO2012/76877, 2012, A1. Location in patent: Page/Page column 97
[5] Patent: US2013/267510, 2013, A1. Location in patent: Paragraph 0708-0710
