反应详情

(5R, 6S)-N-(5-Methanesulfonyloxy-2,2-dimethyl-1,3-dioxepan-6-yl)-3-acetoxy-2-methylbenzamide (compound [9], 786 g, 1.89 mol) was dissolved in dichloromethane (6.29 L), and boron trifluoride diethyl ether (698 ml, 5.68 mol) was added, which was followed by stirring at room temperature for 23 hours. The reaction mixture was cooled to 11° C. and acetic anhydride (268 ml, 2.84 mol) was added, which was followed by stirring at said temperature for 2 hours. The reaction mixture was concentrated to 2.0 kg under reduced pressure and toluene (3.8 L) was added to the obtained residue to give a suspension. N,N-Dimethylethanolamine (571 ml, 5.68 mol) was added to the suspension over 40 minutes at not more than 20° C. Toluene (1.5 L) and water (4.8 L) were added and the mixture was stirred for one hour at room temperature. The organic layer was separated, washed successively with a 10% aqueous citric acid solution (5.00 L) and a 2% aqueous potassium carbonate solution (5.00 L) and dried over magnesium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure to give (2R)-1-acetoxy-2-((4S)-2-(3-acetoxy-2-methylphenyl)-4,5-dihydrooxazol-4-yl)-2-methanesulfonyloxyethane (compound [10′], 1.04 kg) as a dark red oil. 1H-NMR (CDCl3, 300 MHz) δ: 7.68 (d,1H,J=7.7 Hz), 7.26 (t,1H,J=7.9 Hz), 7.14 (d,1H,J=8.0 Hz), 5.02 (dt,1H,J=7.7,3.7 Hz), 4.66 (ddd,1H, J=3.6,8.1,9.5 Hz), 4.53 (dd,1H,J=3.3,12.4 Hz), 4.47-4.38 (m,3H), 3.11 (s,3H), 2.40 (s,3H), 2.34 (s,3H), 2.10 (2,3H)

1. temperatureThe reaction mixture was cooled to 11° C.
2. stirringby stirring
3. customfor 2 hours
4. concentrationThe reaction mixture was concentrated to 2.0 kg under reduced pressure and toluene (3.8 L)
5. additionwas added to the obtained residue
6. customto give a suspension
7. stirringthe mixture was stirred for one hour at room temperature
8. customThe organic layer was separated
9. washwashed successively with a 10% aqueous citric acid solution (5.00 L)
10. dry with materiala 2% aqueous potassium carbonate solution (5.00 L) and dried over magnesium sulfate
11. filtrationThe desiccant was filtered off
12. concentrationthe filtrate was concentrated under reduced pressure