Reaction Steps
N-[4-[(2S)-Tetrahydro-5-oxo-2-furanyl]-phenyl]methanesulfonamide (IIb) from Preparation 3 (9.823 g, 38.5 mmol) was dissolved in a CH2Cl2/toluene (100 ml/41 ml) at 23° C., then cooled to −30° C. The mixture was a slurry. DIBAL-H (59 ml, 1.5 M in toluene) was added slowly to the mixture (1 ml/min). After addition was complete, the solution was stirred until less than 1% of lactone remained by HPLC assay. When the reaction was complete, excess DIBAL-H was pre-quenched with EtOAc (15 ml). This mixture was then added to a pre-cooled (0° C.) aqueous solution of disodium citrate (1.0 M, 200 ml). The reaction mixture was not allowed to warm during this addition period. Ethyl acetate (200 ml) was added, and the resulting two-phase mixture was stirred for at least 5 hours. The organic layer was separated, and the aqueous layer was extracted with EtOAc (2×100 ml). The combined organic layers were washed with brine (2×150 ml). The solvent was removed under reduced pressure. The crude solids were crystallized from ethyl acetate (6 mL/g). A white solid was obtained (8.04 g), having 3% diol by area. Recrystallization from ethyl acetate provided 6.4 g of the title product as a white, powdery solid (64% yield, 93 area %, GT 99% ee). Melting point=129-130° C. 1H NMR (400 MHz, CD3OD) δ 7.42 (d, J=8.2 Hz, 1H), 7.29 (d, J=8.2 Hz, 1H), 7.29 (d, J=8 Hz, 1H), 7.21 (d, J=8.1 Hz, 2H), 5.65 (m, 0.5H), 5.53 (m, 0.5H), 5.14 (t, J=6.9 Hz, 0.5H), 4.93 (t, J=7.6 Hz, 0.5H), 2.92 (s, 3H), 2.49 (m, 1H), 2.25 (m, 1H), 1.98 (m, 1H), 1.92 (m, 1H); 13C NMR (100 MHz, CD3OD) δ C 142.9, 141.2, 140.6, 138.6, 138.5; CH 128.4, 127.9, 121.7, 121.6, 99.9, 99.5, 83.2, 80.3, 74.4, 74.3; CH2 35.5, 35.1, 34.4, 34.2, 33.9; CH3 39.1, 39.0. MS (EI) m/z calcd for C11H15NO4S 257.07 (M+).
