General procedure for the synthesis of (E)-3-(5-nitro-1-cyclohexen-1-yl)acrylic acid from methyl (E)-3-(5-nitro-1-cyclohexen-1-yl)acrylate: to a 1 L methanol solution at 0 °C was added methyl (E)-3-(5-nitro-1-cyclohexen-1-yl)acrylate (67 g, 432 mmol) and Wittig reagent (144.4 g, 432 mmol). The reaction mixture was stirred at 0°C for 3 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was extracted twice with methyl tert-butyl ether (MeOBu-t). The organic phases were combined, filtered to remove insoluble solids, washed with saturated saline and concentrated. The residue was purified by silica gel column chromatography, and 9.2 g of the cis product and 55.1 g (60.4% yield) of the trans product were isolated using hexane/ethyl acetate (10:1, v/v) as eluent. The product structures were confirmed by 1H NMR (CDCl3): δ 7.31 (d, J = 11.3 Hz, 1H), 6.18 (m, 1H), 5.84 (d, J = 15.9 Hz, 1H), 4.74-4.68 (m, 1H), 3.76 (s, 3H), 2.81-2.74 (m, 2H), 2.50-2.04 (m, 4H) . Subsequently, the trans product (2.1 g) was dissolved in a solvent mixture of methanol (9.6 ml) and water (2.4 ml). A 50% aqueous sodium hydroxide solution (0.96 ml) was slowly added dropwise to the solution at about 5°C. After the dropwise addition, the reaction mixture was gradually warmed up to room temperature and stirred for 24 hours. After completion of the reaction, it was neutralized with acetic acid (HOAc) to pH 4-5 and methanol was removed by distillation under reduced pressure. The residue was extracted with ethyl acetate (3 x 50 ml), the organic phases were combined and concentrated to give 1.5 g (76.5% yield) of the target product (E)-3-(5-nitro-1-cyclohexen-1-yl)acrylic acid.
