Acetic Acid → Methyl(1R,2R,5S,6S)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-oxobicyclo[3.1.0]hexane-6-carboxylate

関与物質

反応手順

To a solution of bicyclic mono-TBS-diol 5 (2.08 kg; 6.83 mol) in acetonitrile (8.0 L) at −5° C. was added acetic acid (0.70 L) and water (2.5 L), followed by RuCl3 hydrate (14.20 g). To the mixture was added aqueous sodium hypochlorite solution (˜13%; 7.0 L) over 2 h, keeping the temperature around 0° C. The resulting mixture was stirred at 0° C. for another 1 h until all bicyclic mono-TBS-diol 5 disappeared, monitoring by TLC and NMR. The excess aqueous sodium hypochlorite was decomposed by the addition of isopropanol (0.70 L), aged at 0° C. for 15 min. The two layers were cut and the aqueous layer was discarded. The solution was used for the next reaction without further treatment. Analytical pure sample was obtained by flash silica gel column chromatography (MTBE/hexane) as colorless crystals: mp 70-71° C.; 1H NMR (400 MHz, CDCl3): δ 4.66 (d, J=5.4 Hz, 1H), 3.86 (s, 3H), 3.73 (s, 3H), 2.73 (m, 2H), 2.54 (dt, J=19.1, 5.7 Hz, 1H), 2.22 (dd, J=19.1, 3.8 Hz, 1H), 0.91 (s, 9H), 0.13 (s, 3H), 0.11 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 206.2, 167.1 (d, J=26.1 Hz), 78.9 (d, J=246.4 Hz), 67.6 (d, J=2.8 Hz), 53.4, 47.5 (d, J=3.9 Hz), 42.0 (d, J=11.4 Hz), 39.6 (d, J=13.3 Hz), 25.7, 18.0, −4.76, and −4.78; 19F NMR (376 MHz, CDCl3): δ −210.7; [α]D25=+58.2 (c 0.50, CH3OH).

情報源と証拠