Ammonia → (R)-3-(N,N-Dibenzylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran

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Reaction Conditions

Reaction Steps

(R)-8-Bromo-3-(N,N-dibenzylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran (4.35 g, 9.9 mmol) was dissolved in 45 mL of anhydrous THF and cooled to -78° C. To this was a 1.6M n-BuLi solution (6.8 mL, 10.9 mmol) added dropwise and the mixture was allowed to stir at -78° C. for 1 h. N-Fluorobenzenesulfonimide (3.8 g, 11.9 mmol), dissolved in 30 mL anhydrous THF, was added dropwise over 45 min and allowed to stir at -78° C. for 1 h. The reaction was stopped by adding 3 mL saturated NH4Cl followed by 9 mL of a solution comprised of 2 g of NH2OH×HCl and 8 g of Na2CO3 in 100 mL of H2O and allowing the reaction to warm to room temperature. A 2M NH3 solution was added and the reaction was extracted twice with ether, treated with brine, dried (Na2SO4), filtered, and evaporated in vacuo to give the crude product. Purification of the 8-fluoro (desired) from the 8-hydrogen (15 %) compound was carried out by a crude chromatography (eluent: 25% CH2Cl2 /hexane) to give 1.78 g. The crude product was rechromatographed on silica (eluent: 3% acetone/hexane) to give 1.50 g (40% yield) of the title compound as a clear oil. [α]21D =-112.1° (C=0.1, CHCl3). GC-MS (70 eV) M=377 (37%).

Provenance & Evidence