Sodium hydride → 2-{[(5S)-5-(2,2-diethoxyethoxy)hex-2-yn-1-yl]oxy}tetrahydro-2H-pyran

Sodium hydride (60% in mineral oil, 9.8 g, 240 mmol) was added portion-wise to a 0° C. solution of (2S)-6-(tetrahydro-2H-pyran-2-yloxy)hex-4-yn-2-ol (synthesized as described by G. V. M. Sharma and K. Veera Babu, Tetrahedron: Asymmetry 2007, 18, 2175-2184) (27.0 g, 136 mmol) in tetrahydrofuran (130 mL), at a rate such that the reaction temperature remained below 5° C. After 5 minutes, the cooling bath was removed and the reaction mixture was allowed to stir at room temperature for 3.5 hours, whereupon it was again cooled to 0° C. A solution of 1,1-diethoxy-2-iodoethane (49.9 g, 204 mmol) in tetrahydrofuran (5 mL) was added drop-wise over 30 minutes, at a rate that maintained the reaction temperature below 10° C. After removal of the cooling bath, the reaction mixture was stirred at room temperature for 30 minutes, and then placed in a 50° C. oil bath for 90 minutes, at which time additional 1,1-diethoxy-2-iodoethane (3.3 g, 14 mmol) was added, as a solution in tetrahydrofuran (5 mL). Heating was continued for 1 hour, at which time the reaction mixture was cooled in an ice bath and quenched with a mixture of saturated aqueous ammonium chloride solution (210 mL) and saturated aqueous sodium chloride solution (210 mL). The resulting mixture was extracted with tert-butyl methyl ether (3×200 mL), and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Silica gel chromatography (Gradient: 0% to 50% ethyl acetate in hexanes) afforded the product as a yellow oil. Yield: 22.8 g, 72.5 mmol, 53%. 1H NMR (500 MHz, CDCl3), characteristic peaks: δ 4.80 (t, J=3.5 Hz, 1H), 4.59 (t, J=5.2 Hz, 1H), 4.28 (dt, half of ABX2 pattern, J=15.3, 2.1 Hz, 1H), 4.20 (dt, half of ABX2 pattern, J=15.3, 2.1 Hz, 1H), 3.81-3.87 (m, 1H), 2.48-2.56 (m, 1H), 2.28-2.36 (m, 1H), 1.78-1.88 (m, 1H), 1.69-1.77 (m, 1H), 1.25 (d, J=6.1 Hz, 3H), 1.22 (t, J=7.1 Hz, 6H).