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]+; [α]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, J=12.54 and 3.89 Hz, FmocNCH2 major), 3.26 (1.8H, s, OCH3 major), 3.30 (0.4H, dd, J=12.21 and 4.19 Hz, FmocNCH2 minor), 3.35 (1.2H, s, OCH3 minor), 3.49 (0.6H, m, OCH2CHOH major), 3.52 (0.6H, dd, J=10.04 and 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, J=10.80 and 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).
