A solution of phenylmethyl (3,4-dihydro-1H-2-benzothiopyran-6-yl)carbamate (Step 3, 2.55 g, 8.52 mmol), (1S)-2-(acetylamino)-1-(chloromethyl)ethyl acetate (Tet. Lett. 1996 37 (44) 7737-7740; 3.30 g, 17.03 mmol) and MeOH (0.690 mL, 17.03 mmol) in dry DMF (5.6 mL) under N2 is treated with LiOtBu (1M in hexanes, 25.5 mL, 25.5 mmol) dropwise over 2 hrs, and the resulting biphasic mixture is stirred at ambient temperature for 32 hrs. The mixture is then cooled in an ice bath and treated with glacial HOAc (975 μL), and MeOH (10 mL) is added and the layers are separated. The hexane layer is reextracted with 20% H2O/MeOH (20 mL), and the combined MeOH/H2O phase is diluted with H2O (40 mL) and extracted with EtOAc (3×40 mL). The combined EtOAc phase is then washed with H2O (2×50 mL) and brine (25 mL), dried over MgSO4 and concentrated under reduced pressure, and the residue is chromatographed on a Flash 40M silica gel (90 g, 32-63 μm) cartridge, eluting with a gradient of MeOH/CH2Cl2 (0.5/99.5-3/97). Those fractions with an Rf=0.27 by TLC (MeOH/CHCl3, 5/95) are pooled and concentrated and the product triturated with EtOAc/Et2O to give 1.90 g (73%) of the title compound as an off-white solid, mp 112-114° C. (decomp.). MS (ESI+) for C15H18N2O3S m/z 307 (M+H)+; [α]25D=−24° (c 0.80, DMSO).
