ClC1C=C(C=CC=1)C(OO)=[O:6].[F:12][C:13]1[C:22]2[O:21][CH2:20][C@H:19]([N:23]=CC3C=CC(OC)=CC=3)[CH2:18][C:17]=2[C:16]([O:33][CH3:34])=[CH:15][CH:14]=1.Cl.NO.C([O-])([O-])=O.[Na+].[Na+]>O.CO.C(Cl)Cl>[F:12][C:13]1[C:22]2[O:21][CH2:20][C@H:19]([NH:23][OH:6])[CH2:18][C:17]=2[C:16]([O:33][CH3:34])=[CH:15][CH:14]=1
3 -Chloroperoxybenzoic acid (85%; 7.6 g, 37.6 mmol) was added in portions to a stirred and cooled solution (+4° C.) of (R)-8-fluoro-5-methoxy-3-[N-(4-methoxybenzylidene)-amino]-3,4-dihydro-2H-1-benzopyran (10.8 g, 34 mmol) and methylene chloride (65 mL). The mixture was stirred over night at room temperature. Precipitated 3-chlorobenzoic acid was filtered off and the clear yellow filtrate was concentrated in vacuo. The oily residue was taken up in a solution of hydroxylamine hydrochloride (2.83 g, 40.8 mmol) and anhydrous methanol (60 mL) and the resulting solution was stirred at room temperature for 2 h. The solvent was evaporated to give a thick orange oil. Water was added to the oil, pH was adjusted to 8-9 with saturated aqueous Na2CO3 and the mixture was washed with ether (3×150 mL). The organic phases were combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was flash chromatographed on silica with EtOAc (15 to 50%) in hexane as eluent. The resulting impure product was flash chromatographed a second time on silica with EtOH- CHCl3 (1:99) as eluent to give 6.45 g (89% yield) of the title compound as a colourless crystalline solid. Mp: 111°-113° C. [α]21D =+66.4° (C=1.3; CHCl3). GC-MS (70 eV) M=213 (56%).
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