[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]2[C:11]=1[O:10][CH2:9][C@H:8]([NH2:12])[CH2:7]2.[CH3:15][CH2:16][C:17](=O)[CH2:18][CH3:19].[BH3-]C#N.[Na+].C(O)(=O)C>CO>[NH3:12].[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:13][CH3:14])=[C:6]2[C:11]=1[O:10][CH2:9][C@H:8]([NH:12][CH:17]([CH2:18][CH3:19])[CH2:16][CH3:15])[CH2:7]2To a stirred solution of (R)-8-fluoro-5-methoxy-3-aminochroman (3.13 g, 15.9 mmol) and 3-pentanone (2.2 ml, 20.8 mmol) in 100 ml dry MeOH, NaBH3CN (1.31 g, 20.8 mmol) was added during 10 min. The pH was adjusted to pH was adjusted to pH 6 with acetic acid and the solution was stirred at room temp. After 18 hours, 3-pentanone (0.5 ml, 4.7 mmol) was added and the solution was stirred at room temp. for 3 hours. Concentration and extraction with 100 ml 2M NH3 and 2×250 ml EtOAc, drying of the combined organic phases (Na2SO4) and evaporation gave a crude product that was purified by flash chromatography on silica with hexane:EtOAC:NH3, 60:40:0.5, to give 3.75 g of (R)-8-fluoro-5-methoxy-3-(N-3-pentylamino)chroman as an uncolored oil. [α]D22 -25° (c 1.14 in MeOH).
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