2-Propenoic acid, 3-(5-nitro-1-cyclohexen-1-yl)-, (2E)- synthesis

Yield: 76.5%

Reaction Conditions:

Stage #1:C₁₀H₁₃NO₄ with sodium hydroxide in methanol;water at 5 - 20; for 24 h;
Stage #2: with acetic acid in methanol;water; pH=4 - 5

Steps:

2
To a solution of 10 (67 g, 432 mmol) in 1 L of methanol at 0 ⁰C was added 144.4 g (432 mmol) of the Wittig reagent. The resulting mixture was agitated at 0 ⁰C for 3 hrs. The solvent was removed under reduced pressure. The residue was extracted with MeOBu -t twice. The extract was filtered to remove any solid, washed with brine, and concentrated. The residue was chromatographed on a silica gel column, eluting with hexane/ethyl acetate (10/ 1) to give 9.2 g cis and 55.1 g (60.4%) trans product. ¹H NMR (CDCl₃) d 7.31 (d, J = 11.3 Hz, IH), 6.18 (m, IH), 5.84 (d, J = 15.9 Hz, IH), 4.74-4.68 (m, IH), 3.76 (s, 3H), 2.81-2.74 (m, 2H), 2.50-2.04 (m, 4H).Next, to a flask were added 2.1 g of the methyl ester, 9.6 ml of MeOH and 2.4 ml of water. To the mixture at about 5 ⁰C was added dropwise 0.96 ml of 50% NaOH. The mixture was allowed to warm to room temperature and stirred at this temperature for about 24 hrs. The reaction mixture was neutralized with HOAc to pH between 4 and 5 and the methanol was removed under reduced pressure. The residue was extracted with 3 X 50 ml EtOAc. The EtOAc layer was concentrated to EPO give 1.5 g of nitroacid 6 (76.5%).

References:

SCHERING CORPORATION;WU, George, G.;SUDHAKAR, Anantha;WANG, Tao;XIE, Ji;CHEN, Frank, Xing;POIRIER, Marc;HUANG, Mingsheng;SABESAN, Vijay;KWOK, Daw-long;CUI, Jian;YANG, Xiaojing;THIRUVENGADAM, Tiruvettipuram, K.;LIAO, Jing;ZAVIALOV, Ilia;NGUYEN, Hoa, N.;LIM, Ngiap Kie WO2006/76415, 2006, A2 Location in patent:Page/Page column 35-37