Reaction Steps
A solution of sodium carbonate (239 mg, 2.26 mmol) in water (10 mL) was added whilst stirring to a solution of (3R,3aR,6S,6aS)-6-methoxyhexahydro-2H-furo[3,2-b]pyrrol-3-ol in 1,4-dioxane (7 mL). A solution of 9-fluorenylmethoxycarbonyl chloride (319 mg, 1.23 mmol) in 1,4-dioxane (3 mL) was added then the mixture stirred for 40 minutes then water (30 mL) was added and the product extracted into dichloromethane (1×40 mL then 2×30 mL). The organic layer was washed with brine (50 mL), then dried (MgSO4), filtered and reduced in vacuo to leave a residue. Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 7:93 to 45:55 gave bicyclic alcohol (6b) (270 mg, 66%) as a white solid. TLC (Rf=0.34, EtOAc:heptane 3:2), analytical HPLC single main peak, Rt=15.990 min., HPLC-MS 382.1 [M+H]+, 404.1 [M+Na]+, 785.3 [2M+Na]+; [□]D18.5−35.4° (c=2.758, CHCl3); δH (500 MHz, CDCl3) mixture of rotamers major:minor 3:2; 1.02 (0.6H, d, J=3.55 Hz, OH major), 2.59 (0.40H, d, J=3.19 Hz, OH minor), 3.10 (0.6H, dd, 3.89 Hz, FmocNCH2 major), 3.26 (1.8H, s, OCH3 major), 3.30 (0.4H, dd, 4.19 Hz, FmocNCH2 minor), 3.35 (1.2H, s, OCH3 minor), 3.49 (0.6H, m, OCH2CHOH major), 3.52 (0.6H, dd, 1.81 Hz, OCH2CHOH major), 3.55-3.59 (1.2H, m, OCH2CHOH major and FmocNCH major), 3.64 (0.6H, d, J=3.69 Hz, CHOCH3 major), 3.65-3.70 (1H, m, FmocNCH2), 3.75-3.79 (0.8H, m, OCH2CHOH minor and CHOCH3 minor), 3.85 (0.4H, dd, J=9.85 and 4.46 Hz, OCH2CHOH minor), 4.22-4.26 (1.4H, m, FmocNCH minor and Fmoc CH), 4.37 (0.6H, d, J=4.64 Hz, OCHCHOCH3 major), 4.40-4.44 (1.2H, m, Fmoc CH2 minor and OCH2CHOH minor), 4.60 (0.4H, d, J=4.94 Hz, OCHCHOCH3 minor), 4.70 (0.6H, dd, J=10.80 and 3.96 Hz, Fmoc CH2 major), 4.82 (0.6H, dd, 4.25 Hz, Fmoc CH2 major), 7.29-7.80 (8H, Fmoc aromatic CH); δC (125 MHz, CDCl3) 47.248/47.378 (Fmoc CH), 49.754/50.177 (FmocNCH2), 56.868/56.996 (OCH3), 65.736/67.270 (Fmoc CH2), 68.262/69.085 (FmocNCH), 73.760/74.008 (OCH2CHOH), 75.812/76.145 (OCH2CHOH), 81.509/82.286 (OCHCHOCH3), 83.496/84.166 (OCHCHOCH3), 119.805, 119.982, 120.003, 124.494, 124.576, 124.958, 124.975, 127.019, 127.034, 127.404, 127.488, 127.637, 127.726, 127.754 and 127.865 (Fmoc aromatic CH), 143.633, 143.909, 143.943 and 144.037 (Fmoc quaternary), 154.255/155.025 (Fmoc C═O).
