Synthesis
(1R,4S)-4-Aminocyclopent-2-ene-1-carboxylic acid (130 g, 1.0 mol) was dissolved in a solvent mixture of water (250 mL) and THF (750 mL) and sodium bicarbonate (170 g, 2.0 mol) was added. After stirring for 30 minutes, solid di-tert-butyl dicarbonate (230 g, 1.05 mol) was slowly added. The reaction mixture was stirred overnight at room temperature. Upon completion of the reaction, the insoluble material was removed by filtration and THF was removed by evaporation.The residue was cooled to 0 °C and the pH was adjusted to 3 by slow addition of aqueous 2N HCl (ca. 500 mL).The precipitated white solid was collected by filtration, washed with water, and dried under vacuum overnight to afford (1R,4S)-4-((tert-butoxycarbonyl)amino)cyclopent-2-enecarboxylic acid (230 g, 100%). The product was characterized by 1H NMR (400 MHz, CD3OD): δ 5.95 (m, 1H), 5.79 (m, 1H), 4.80 (br s, 1H), 3.45 (m, 1H), 2.50 (m, 1H), 1.79 (m, 1H), 1.44 (s, 9H).
References
[1] Patent: WO2004/76411, 2004, A2. Location in patent: Page 27-28
[2] Patent: WO2003/93231, 2003, A2. Location in patent: Page/Page column 55-56
[3] Patent: US2007/155731, 2007, A1. Location in patent: Page/Page column 27
[4] Patent: US2007/155731, 2007, A1. Location in patent: Page/Page column 35
[5] Patent: WO2005/110409, 2005, A2. Location in patent: Page/Page column 30
