反应详情

Titanium tetrachloride (15.8 mL, 144 mmol) was added over 5 minutes to a vigorously stirred solution of N-propionyl-2-benzoxazolone (25.0 g, 131 mmol) in anhydrous CH2Cl2 (250 mL) cooled on ice and maintained under inert atmosphere. After 10 minutes, the yellow slurry was treated with N-methylmorpholine (15.8 mL, 144 mmol) over 5 minutes, and stirring was continued for an additional 45 minutes. A 0.48 M solution of 3-fluoropropanal (310 mL, 150 mmol) was added to the dark red solution over 30 minutes, such that the internal temperature remained below 10° C. After addition was complete, the mixture was stirred for an additional 30 minutes on ice, then at warm to ambient temperature an additional 1 hour. The reaction was treated with 250 mL of 2 N HCl with vigorous mixing, and the phases were separated, discarding the aqueous phase. The organic phase was filtered through a pad of silica gel (10 g), which was subsequently washed with 100 mL of methyl tert-butyl ether (MTBE). The combined eluates were evaporated to dryness. The resulting solid mass was triturated with MTBE, allowed to stand for 1 hour, then collected by vacuum filtration, yielding 26 gm of crystalline product. 1H-NMR: δ 8.07-8.02 (m, 1H), 7.29-7.18 (m, 3H), 4.77-4.05 (m, 2H), 4.31 (m, 1H), 3.96 (dq, J=7, 3 Hz, 1H), 2.00-1.79 (m, 2H), 1.34 (d, J=7 Hz, 3H). 13C-NMR: δ 176.1, 151.1, 142.2, 127.7, 125.6, 125.0, 116.2, 110.0, 82.0, 80.4, 68.0, 43.8, 34.7, 34.5, 10.4.

1. temperaturecooled on ice
2. temperaturemaintained under inert atmosphere
3. waitwas continued for an additional 45 minutes
4. customremained below 10° C
5. additionAfter addition
6. stirringthe mixture was stirred for an additional 30 minutes on ice
7. customthe phases were separated
8. filtrationThe organic phase was filtered through a pad of silica gel (10 g), which
9. washwas subsequently washed with 100 mL of methyl tert-butyl ether (MTBE)
10. customThe combined eluates were evaporated to dryness
11. customThe resulting solid mass was triturated with MTBE
12. waitto stand for 1 hour
13. filtrationcollected by vacuum filtration