反应详情

Benzo[b]-thien-3-ylglyoxylic acid (2.27 g) and benzyloxyamine hydrochloride (1.915 g) were dissolved in ethanol (70 ml) and water (30 ml). The solution was adjusted to pH 4.5 with 40% w/v sodium hydroxide solution and stirred at this pH for 2 hr. The solution was stood overnight and adjusted to pH 9 then washed with ether. The aqueous phase was acidified under ethyl acetate and the organic layer was washed with water, saturated brine and dried. Evaporation gave a mixture of syn and anti-isomers as a buff crystalline solid (3.4 g., 99%). The crude acid in ether was treated with excess diazomethane in ether at 0°-5°. The excess reagent was destroyed with acetic acid and the ether solution was washed with sodium bicarbonate, water and dried. Evaporation gave a pale brown oil (3.34 g., 93%). The crude product in methanol (100 ml.) was treated with sodium hydroxide solution (1N, 10 ml) at room temperature for 1 hr. The hydrolysis was followed by thin layer chromatography on silica. Hydrochloric acid (2N 5 ml.) was added to stop the hydrolysis and methanol was removed by evaporation. Ethyl acetate was added and the anti-2-benzyloxyimino-2-(benzo[b]-thien-3-yl)acetic acid was removed by washing with sodium bicarbonate. The ethyl acetate layer was washed with water and dried and evaporated to a pale orange oil (1.99 g., 56%). This was treated in methanol (90 ml.) with sodium hydroxide (1N; 10 ml) at room temperature for 7 hr. A further aliquot of sodium hydroxide (1N; 5 ml) was added and the solution stood for 2 days to complete hydrolysis. The methanol was removed by evaporation and the residue dissolved in ethyl acetate and water. The mixture was adjusted to pH 1.5 and the ethyl acetate layer was washed with water, saturated brine and dried. Evaporation gave yellow crystals (1.82 g. 50%) Crystallisation from a mixture of benzene and cyclohexane gave the title compound as pale orange crystals (1.29 g., 36%), m.p. 120.5°-121°, λmax. (EtOH) 232, 285.5, 296.5 306.5 nm. (ε22,500, 11,800, 11,500, 10,400), τ values (DMSO-d6) include 1.90, 1.97, 2.3-2.7 (aromatic protons), 4.64 (CH2 singlet).

1. waitThe solution was stood overnight
2. washthen washed with ether
3. washthe organic layer was washed with water, saturated brine
4. customdried
5. customEvaporation
6. customgave
7. additiona mixture of syn and anti-isomers as a buff crystalline solid (3.4 g., 99%)
8. customThe excess reagent was destroyed with acetic acid
9. washthe ether solution was washed with sodium bicarbonate, water
10. customdried
11. customEvaporation
12. customgave a pale brown oil (3.34 g., 93%)
13. customwas removed by evaporation
14. additionEthyl acetate was added
15. customthe anti-2-benzyloxyimino-2-(benzo[b]-thien-3-yl)acetic acid was removed
16. washby washing with sodium bicarbonate
17. washThe ethyl acetate layer was washed with water
18. customdried
19. customevaporated to a pale orange oil (1.99 g., 56%)
20. additionThis was treated in methanol (90 ml.) with sodium hydroxide (1N; 10 ml) at room temperature for 7 hr
21. additionA further aliquot of sodium hydroxide (1N; 5 ml) was added
22. waitthe solution stood for 2 days
23. customhydrolysis
24. customThe methanol was removed by evaporation
25. dissolutionthe residue dissolved in ethyl acetate
26. washthe ethyl acetate layer was washed with water, saturated brine
27. customdried
28. customEvaporation
29. customgave yellow
30. customcrystals (1.82 g. 50%) Crystallisation
31. additionfrom a mixture of benzene and cyclohexane