反应详情

To a stirred solution of 5 (20 g, 0.11 mol) in CH2Cl2 (250 mL) at 0° C. was added TiCl4 (49.2 g, 28.5 mL, 0.26 mol) in CH2Cl2 (50 mL). Stirring was continued at 0° C. while a solution of MeOCHCl2 (14.6 g, 11.5 mL, 0.127 mol) was added dropwise over 30 min. When the addition was complete, the solution was warmed to room temperature, left to stand for 30 min, and concentrated to half-volume by rotary evaporation. The resulting solution, containing the α-chloro ether 6, was poured into a mixture of ice (250 g) and 12 N HCl (10 mL), and then EtOAc (200 mL) was added. The two-phase mixture was stirred vigorously for 30 min, the layers were separated, the aqueous layer was back-extracted with EtOAc, and the combined EtOAc extracts were evaporated to dryness. Recrystallization of the crude solid (24.2 g) from a mixture of isooctane and absolute EtOH afforded 2-methoxy-5-(methoxycarbonyloxy) benzaldehyde (7) as white needles (17.7 g, 77%); mp 88–89° C. (lit. mp 88–90° C. 1H NMR (CDCl3) δ 3.90 (s, 3H, MeO), 3.92 (s, 3H, MeO), 6.99 (d, J=9 Hz, 1H, aryl 3-H), 7.38 (dd, J=9 Hz, J=3 Hz, 1H aryl 4-H), 7.63 (d, J=3 Hz, 1H, aryl 6-H), 10.45 (s, 1H, CH═O). Evaporation of the supernatant from the first crop afforded an additional 5.3 g (23%), bringing the total to 23 g (100%). The two fractions were combined and used without further purification.

1. additionwas added dropwise over 30 min
2. additionWhen the addition
3. waitleft
4. concentrationconcentrated to half-volume by rotary evaporation
5. additionThe resulting solution, containing the α-chloro ether 6
6. additionwas poured into a mixture of ice (250 g) and 12 N HCl (10 mL)
7. additionEtOAc (200 mL) was added
8. stirringThe two-phase mixture was stirred vigorously for 30 min
9. customthe layers were separated
10. extractionthe aqueous layer was back-extracted with EtOAc
11. customthe combined EtOAc extracts were evaporated to dryness
12. customRecrystallization of the crude solid (24.2 g)
13. additionfrom a mixture of isooctane and absolute EtOH