Reaction Steps
(2S)-Methyl 2-(2-chlorophenyl)-2-(2-oxo-7,7a-dihydrothieno[3.2-c]pyridin-5(2H,4H,6H)-yl)-acetate (IV-1) (85 mg) was dissolved in 10 ml of anhydrous tetrahydrofuran, and 0.141 ml of triethylamine was added at room temperature and stirred for 10 min. Then, 0.167 ml of ethyl chloroformate was added dropwise at 0° C. After the addition, the reaction solution became a light yellow cloudy solution from a dark red clear solution. The ice bath was removed and the reaction was warmed to 10° C. for 1 hr. Then, 0.07 ml of triethylamine and 0.1 ml of ethyl chloroformate were additionally added in an ice bath at 0° C. The ice bath was removed and the reaction was warmed to 10° C. for 1 hr, at which the raw materials substantially disappeared. Water (20 ml) was added, the reaction solution was extracted with ethyl acetate (30 ml×3) and dried over anhydrous sodium sulfate, and the solvent was evaporated to give a crude product, which was subjected to flash column chromatography (petroleum ether:ethyl acetate=40:3) to obtain (S)-methyl 2-(2-(ethoxycarbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate (I-14) (77 mg). Yield 75%, mp: 42-44° C., ee=97.3% (chiral HPLC analysis conditions were the same as those in Example 4), [α]D20=+40.00° (c 0.50, MeOH); 1H-NMR (300 MHz, CDCl3) δ 1.37 (t, 3H, J=7.2 Hz), 2.76-2.78 (m, 2H), 2.86-2.90 (m, 2H), 3.52 (d, 1H, J=14.2 Hz), 3.64 (d, 1H, J=14.3 Hz), 3.72 (s, 3H), 4.32 (q, 2H, J=7.1, 14.3 Hz), 4.90 (s, 1H), 6.30 (s, 1H), 7.24-7.68 (m, 4H); 13C-NMR (75 MHz, CDCl3) δ 14.4, 25.4, 48.4, 50.5, 52.4, 65.7, 68.1, 112.7, 126.2, 127.4, 129.7, 129.8, 130.1, 130.2, 134.0, 135.0, 152.9, 157.3, 171.5; ESI-MS m/z 410.1 [M+H]+, 432.1 [M+Na]+; HRMS Calcd for C19H21NO5SCl [M+H]+ m/z 410.0836. found 410.0829.
