Acetic Acid → (R)-3-(N-Cyclobutyl-N-isopropylamino)-8-fluoro-5-methoxy-3,4-dihydro-2H-1-benzopyran

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Reaction Steps

(R)-8-Fluoro-3-(N-isopropylamino)-5-methoxy-3,4-dihydro-2H-1-benzopyran (1.96 g, 8.19 mmol) was dissolved in anhydrous methanol (20 mL) and to this was cyclobutanone (6.1 mL, 81.9 mmol) added. The reaction was cooled (ice-bath) then sodium cyanoborohydride (2.0 g, 16.4 mmol) was added, the pH was adjusted to 4-5 with acetic acid, 3 Å molecular sieves were added and the reaction was allowed to stir at room temperature overnight. After 24 h the pH-was again adjusted to 4-5 and the reaction was allowed to stir for 3 more days. The reaction was filtered, solvent was removed in vacuo, the remains were taken into a 2M solution of NH3 and then extracted thrice with diethyl ether. The combined ether portions were dried (MgSO4) filtered, and the solvent removed in vacuo to give the crude residue. Chromatography on silica (eluent: 10% ethyl acetate/hexane) gave 1.60 g (77% yield) of the title compound as a clear oil. [α]21D =-95.1° (C=0.1; CHCl3). GC-MS (70 eV) M=293 (3%).

Provenance & Evidence