反应详情

15.3 g of (6R,7R)-7-[2-[2-(2-chloroacetamido)-4-thiazolyl]-2-[(Z)-methoxyimino]acetamido]-3-[[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (Fraction I) are suspended in 150 ml of water together with 5 g of thiourea. While gassing well with nitrogen and stirring, the pH is adjusted to 6.8-7.0 with saturated sodium hydrogen carbonate solution, an orange coloured solution resulting. The pH of the solution is held constant at 6.8 for 6 hours by means of an autotitrator with the addition of sodium hydrogen carbonate solution. A further 2.5 g of thiourea are added and the solution is stirred for a further 3 hours, the pH being held at 6.8 with the addition of saturated sodium hydrogen carbonate solution. The red solution is stored overnight in a refrigerator, the solution becoming darker. The pH of the solution is adjusted to 2.0-2.5 by the addition of 100% formic acid, a substance separating. This substance is filtered off under suction and washed with 100 ml of 10% aqueous formic acid. The mother liquor is discarded. The brownish material on the suction filter is suspended in 200 ml of water and the pH is adjusted to 7 with triethylamine, a brown solution resulting. This solution is stirred with 2 g of active carbon for 30 minutes, the carbon is filtered off and the still brown filtrate is adjusted to pH 3.5 with 100% formic acid while stirring well. The substance which thereby separates is filtered off under suction, washed with 50 ml of 10% aqueous formic acid and discarded. The dark yellow filtrate is adjusted to pH 2-2.5 with 100% formic acid, a substance separating. This substance is filtered off under suction, washed with ice/water and dried. The cephalosporanic acid obtained is converted into the disodium salt by suspension in a mixture of 40 ml of acetone and 40 ml of water and treatment with 20 ml of a 2 N solution of 2-ethylcaproic acid sodium salt in ethyl acetate. To the thereby resulting orange coloured solution are added 50 ml of acetone, there separating a brown resin which is filtered off. The yellow filtrate is stirred for 30 minutes, the disodium salt crystallising. The mixture is treated portionwise with a further 50 ml of acetone and stored overnight in a refrigerator. The crystallisate is filtered off under suction, washed successively with acetone/water (85:15), pure acetone and low-boiling petroleum ether and dried at 40° C. overnight in vacuo. There is obtained the disodium salt of (6R,7R)-7-[2-(2-amino-4-thiazolyl)-2-[(Z)-methoxyimino]acetamido]-3-[[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid in the form of beige coloured crystals; [α]D20 =-144° (c=0.5 in water). The nuclear magnetic resonance spectrum and the microanalysis correspond to the given structure.

1. customan orange coloured solution resulting
2. stirringthe solution is stirred for a further 3 hours
3. customa substance separating
4. filtrationThis substance is filtered off under suction
5. washwashed with 100 ml of 10% aqueous formic acid
6. filtrationThe brownish material on the suction filter
7. customa brown solution resulting
8. stirringThis solution is stirred with 2 g of active carbon for 30 minutes
9. filtrationthe carbon is filtered off
10. stirringwhile stirring well
11. filtrationThe substance which thereby separates is filtered off under suction
12. washwashed with 50 ml of 10% aqueous formic acid
13. customa substance separating
14. filtrationThis substance is filtered off under suction
15. washwashed with ice/water
16. customdried