反应详情

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 add was filtered off and the dear 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%).

1. stirringThe mixture was stirred over night at room temperature
2. customPrecipitated 3-chlorobenzoic
3. additionadd
4. filtrationwas filtered off
5. concentrationthe dear yellow filtrate was concentrated in vacuo
6. stirringthe resulting solution was stirred at room temperature for 2 h
7. customThe solvent was evaporated
8. customto give a thick orange oil
9. washthe mixture was washed with ether (3×150 mL)
10. washwashed with brine
11. dry with materialdried (Na2SO4)
12. filtrationfiltered
13. concentrationconcentrated in vacuo
14. customchromatographed on silica with EtOAc (15 to 50%) in hexane as eluent
15. customchromatographed a second time on silica with EtOH- CHCl3 (1:99) as eluent