反应详情

温度

-78 °C

To a solution of phosphine oxide 5 (13 mg, 0.0218 mmol) in anhydrous THF (130 μL) at 0° C. was slowly added PhLi (18 μL, 0.0327 mmol) under argon with stirring. The solution turned deep orange. The mixture was cooled to −78° C. and a precooled (—78° C.) solution of protected hydroxy ketone 4 (8.5 mg, 0.0262 mmol) in anhydrous THF (170 μL) was slowly added. The mixture was stirred at −78° C. for 2 h 30 min and then at 0° C. for 18 h. Ethyl acetate was added and the organic phase was washed with brine, dried (MgSO4) and evaporated. The residue was dissolved in hexane, applied on a silica Sep-Pak cartridge, and washed with hexane/ethyl acetate (99.7:0.3, 20 mL) to give 19-nor-vitamin D derivative 6. The vitamin derivative was further purified by HPLC (250×10 mm Zorbax-Sil column, 4 mL/min) using hexane/ethyl acetate (99.9:0.1) solvent system. Pure compound 6 was eluted at RV 22 mL as a colorless oil: UV (in ethanol) λmax 244, 252, 262 nm; 1H NMR (CDCl3) δ 0.026, 0.047, 0.065 and 0.079 (each 3H, each s, 4×SiCH3), 0.559 (3H, s, 18-CH3), 0.593 (6H, q, 3×SiCH2), 0864 and 0.894 (each 9H, each s, 2×Si-t-Bu), 0.966 (9H, t, 3×SiCH2CH3), 1.019 (3H, d, J=6.5 Hz, 21-CH3), 3,25 (1H, dd, J=9.5, 7.9 Hz, 22-H), 3.62 (11H, dd, J=3.4, 9.6 Hz, 22-H), 4.42 (2H, m, 1α-H, 3β-H), 4.92 and 4.96 (each 11H, each s, ═CH2), 5.84 (1H, d, J=11.2 Hz, 7H) and 6.21 (1H, d, J=11.2 Hz, 6-H); MS m/z (relative intensity): 688 (M+, 34), 659 (M+-CH3), 557 (M+-OSi(CH3)2t-Bu, 50).

1. customat 0° C.
2. stirringThe mixture was stirred at −78° C. for 2 h 30 min
3. washthe organic phase was washed with brine
4. dry with materialdried (MgSO4)
5. customevaporated
6. dissolutionThe residue was dissolved in hexane
7. washwashed with hexane/ethyl acetate (99.7:0.3, 20 mL)