反应详情

温度

-73 °C

To a cooled (-73° C.), stirred solution of 1.04 g. of benzhydryl 7-(2-thienylacetamido)-3-formyl-2-cephem-4-carboxylate and 8 ml. of tetrahydrofuran was added 2.4 ml. of a 2.5 molar phenylmagnesium bromide solution. After stirring the reaction mixture with cooling for four minutes, 8 ml. of 1N.HCl was added, and the reaction mixture was allowed to warm to 0°. Ethyl acetate was added, and the reaction mixture was then washed twice with cold 1 N.HCl, and twice with brine and then dried over anhydrous sodium sulfate. Evaporation in vacuo to dryness gave a residue which was chromatographed on a silica gel column using a toluene-ethyl acetate gradient. This chromatography failed to separate the unreacted starting material (3-formyl-2-cephem ester) and the product cephem secondary carbinol. Combining the fractions off the column and evaporating in vacuo to dryness gave 0.895 g. of a mixture which was dissolved in 50 ml. of acetone and reacted with 0.77 ml. of a 2.26 molar solution of chromic acid. This reaction mixture was allowed to stir for 15 minutes at room temperature after which time 5 ml. of isopropanol was added. After five minutes the reaction mixture was evaporated in vacuo to dryness, and the residue was dissolved in an ethyl acetate/water slurry and then transferred to a separatory funnel with the aid of ethyl acetate. The organic layer was separated and washed with water (4X) and brine (2X) and then dried over anhydrous sodium sulfate. Evaporation in vacuo to dryness and chromatography of the residue thereby obtained on silica using a toluene-ethyl acetate gradient provided 0.213 g. of the 3-formyl-2-cephem starting material and 0.366 g. (41 percent) of the title product which crystallized from methylene chloride hexane as white needles (m.p. 179°-180°):

1. stirringAfter stirring the reaction mixture
2. temperaturewith cooling for four minutes
3. temperatureto warm to 0°
4. washthe reaction mixture was then washed twice with cold 1 N
5. dry with materialHCl, and twice with brine and then dried over anhydrous sodium sulfate
6. customEvaporation in vacuo to dryness
7. customgave a residue which
8. customwas chromatographed on a silica gel column
9. customto separate the unreacted starting material (3-formyl-2-cephem ester)
10. customevaporating in vacuo to dryness
11. customgave 0.895 g
12. dissolutionof a mixture which was dissolved in 50 ml
13. stirringto stir for 15 minutes at room temperature after which time 5 ml
14. customAfter five minutes the reaction mixture was evaporated in vacuo to dryness
15. dissolutionthe residue was dissolved in an ethyl acetate/water slurry
16. customtransferred to a separatory funnel with the aid of ethyl acetate
17. customThe organic layer was separated
18. washwashed with water (4X) and brine (2X)
19. dry with materialdried over anhydrous sodium sulfate
20. customEvaporation in vacuo to dryness and chromatography of the residue
21. customthereby obtained on silica using a toluene-ethyl acetate gradient
22. customprovided 0.213 g
23. custom(41 percent) of the title product which crystallized from methylene chloride hexane as white needles (m.p. 179°-180°)