(84%) of 7: 1H NMR (300 MHz, CDCl3) d 7.22-7.20 (m, 1H), 6.98-6.91 (m, 2H), 5.21 (ddd, 1H, J 8.2, 3.2, and 0.7 Hz), 3.56 (brs, 2H), 3.01-2.83 (m, 2H), 2.45(s, 3H), 2.04-1.83 (m, 2H); 13C NMR (75 MHz, CDCl3) d 149.7, 126.5, 123.7, 122.3, 72.1, 50.2, 36.8, 35.9; EIMS (70eV) m/z (rel intensity) 171 (M+, 35), 139 (22), 128 (100), 111(31); [a]D20 = -10.8 (c 0.52, MeOH); lits. for its enantiomer [a]D22 = +9.74 (c 3.8, MeOH),7a [a]D34 = +13.9 (c 2.4, MeOH).7b
(S)-Duloxetine (8). To a solution of 7 (171 mg, 1 mmol) in DMSO (5 ml), were added sodium hydride (36 mg 1.5 mmol) and then 1-fluoronaphthalene (190 mg, 1.3mmol). After stirring for 8h, the reaction mixture was partitioned with ethyl acetate and water. After an extractive workup, the combined organic layers were dried over sodium sulfate and then concentrated in vacuo. The residue was purified by flash chromatography (ammonium hydroxide/methanol/ dichloromethane, 0.1/1/4) to yield 232 mg (78%) of 8: 1H NMR (300 MHz, CDCl3) d 8.37-8.33 (m, 1H), 7.79-7.74 (m, 1H), 7.50-7.44 (m, 2H), 7.39-7.37 (m, 1H), 7.28-7.18 (m, 2H), 7.05-7.04 (m, 1H), 6.93-6.90 (m, 1H), 6.86-6.84 (m, 1H), 5.78 (dd, 1H, J 7.6 and 5.3 Hz ), 2.86-2.78 (m, 2H), 2.50-2.39 (m, 4H), 2.27-2.16 (m, 1H); 13C NMR (75 MHz, CDCl3) d 153.3, 145.2, 134.5, 127.4, 126.5, 126.2, 126.1, 125.7, 125.2, 124.6, 124.5, 122.1, 120.5, 106.9, 74.7, 48.3, 39.0, 36.5; EIMS (70eV) m/z (rel intensity) 297 (M+, 4), 187 (80), 153 (69), 144 (100); [a]D20 = +110.5 (c 1.1, MeOH); lit.7b [a]D30 = +114 (c 1, MeOH); lit.15b [a]D20 = +112 (c 1, MeOH); HPLC analysis: 95% ee (Chiralcel OD-H, hexane/PriOH, 85/15, 0.5 ml/min; tR (S) 18 min, tR (R) 25 min.
Acknowledgements
This work was supported by a grant for Industrial Technology Development Programs from the Korea Research Institute of Chemical Technology (BS.F-0801).
References
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