| 76.5% |
Stage #1: With sodium hydroxide In methanol; water at 5 – 20℃; for 24.00 h;
Stage #2: With acetic acid In methanol; water |
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 (60.4percent) 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 50percent 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 (76.5percent). |