Reaction Steps
A 2M solution of the borane-dimethylsulphide complex in THF (1.72 ml, 3.44 mmoles) is added drop wise to the [3-(5-chlorofuran-2-yl)-4-phenylisoxazol-5-yl]carboxylic acid (500 mg, 1.73 mmoles) solubilised in anhydrous THF (6 ml) and kept stirring at 0° C. in an atmosphere of N2. The reaction mixture is brought to ambient temperature and kept stirring. After 15 hours more BMS is added (1.72 ml), and after 9 more hours the reaction is blocked by adding H2O (10 ml), NaOH 3N (10 ml) and H2O2 (30% w/w, 10 ml). The mixture is kept stirring for 30 minutes. The two phases are separated and the aqueous phase is extracted three times with ethyl acetate. The combined organic extracts are dried over Na2SO4 and the solvent distilled in a vacuum. The residue (470 mg) subjected to column chromatography (silica gel, petroleum ether/ethyl acetate=9:1 until 1:1, modified with the elution of the products) gives the product which is crystallised cold from ethyl acetate/hexane (1:1) with a final yield of 52%, the equivalent of 248 mg. M.p. 102-103° C. FT-IR (KBr): 3600-3210, 3144, 3128, 3054, 2927, 1594, 1511, 1447, 1405, 1356, 1289, 1216, 1129, 1019, 1010, 942, 925, 902, 802, 769, 702 cm−1. 1H NMR (400 MHz, CDCl3, δ): 7.45-7.41 (m, 3H, aromatic protons); 7.35-7.30 (m, 2H, aromatic protons); 6.28 (d, J=3.4 Hz, 1H, furyl proton); 6.12 (d, J=3.4 Hz, 1H, furyl proton); 4.65 (s, 2H, CH2OH); 2.30-2.05 (bs, 1H, OH: exchange with D2O). 13C NMR (100 MHz, CDCl3, δ): 167.6, 152.5, 143.2, 138.9, 130.2, 129.1, 129.0, 128.5, 116.6, 114.3, 108.2, 54.8. GC-MS (70 eV) m/z (rel.int.): 277 [M(37Cl)+, 33], 275 [M(35Cl)+, 100], 246 (12), 244 (32), 238 (14), 218 (14), 217 (16), 216 (32), 212 (29), 211 (31), 190 (21), 188 (58), 183 (10), 182 (11), 180 (10), 154 (42), 153 (38), 152 (35), 129 (18), 128 (14), 127 (25), 91 (14), 89 (42), 77 (13), 63 (11). Anal. Calc. for C14H10ClNO3: C, 60.99; H. 3.66; N, 5.08. Found: C, 61.00; H, 3.62; N, 5.06.
