Dimethylformamide → HCID 12834178, compound

Temperature

50 °C

A mixture of dimethylformamide (0.805 g) and thionyl chloride (1.55 g) was warmed for 30 minutes at 50° C. with enough shaking, and then excess thionyl chloride was removed under reduced pressure. The residual crystals were washed twice with a small amount of absolute ether, and then ether was removed under reduced pressure. The residual crystals were dissolved in dried dichloromethane (40 ml), and to the solution was added at 0° C. thienylglycolic acid (0.95 g). The mixture was cooled at -50° C., and to the mixture was dropwise added over 30 minutes a solution of triethylamine (1.11 g) in dried dichloromethane (10 ml), after which the mixture was stirred for 30 minutes at the same temperature. To the solution was dropwise added over 30 minutes at -50° C. a solution which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (1.075 g), bis(triethylsilyl)acetamide (2.04 g) and dried dichloromethane (25 ml) for 2 hours at room temperature. The mixture was stirred for 2 hours at the same temperature and for 1 hour at -20° to -30° C. After the reaction, water (10 ml) was added at 0° C. to the reaction mixture, and then dichloromethane was removed under reduced pressure. To the residue was added water (40 ml), after which the solution was extracted twice with ethyl acetate (50 ml). The extract was extracted three times with a sodium bicarbonate aqueous solution (50 ml), and the aqueous extract was washed with ethyl acetate (50 ml), adjusted to pH 2 with 5% sulfuric acid and extracted three times with ethyl acetate (30 ml), after which the extract was washed with water and dried. After the solvent was distilled off, the residue was pulverized by adding isopropyl ether to give pale yellow powder of 2-methyl-7-[2-hydroxy-2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid (1.32 g), mp 91° to 96° C. (dec.).

1. customexcess thionyl chloride was removed under reduced pressure
2. washThe residual crystals were washed twice with a small amount of absolute ether
3. customether was removed under reduced pressure
4. dissolutionThe residual crystals were dissolved in dried dichloromethane (40 ml)
5. additionto the solution was added at 0° C. thienylglycolic acid (0.95 g)
6. temperatureThe mixture was cooled at -50° C.
7. additionto the mixture was dropwise added over 30 minutes a solution of triethylamine (1.11 g) in dried dichloromethane (10 ml)
8. additionTo the solution was dropwise added over 30 minutes at -50° C. a solution which
9. customwas prepared
10. stirringby stirring
11. stirringThe mixture was stirred for 2 hours at the same temperature and for 1 hour at -20° to -30° C
12. additionwas added at 0° C. to the reaction mixture
13. customdichloromethane was removed under reduced pressure
14. additionTo the residue was added water (40 ml)
15. extractionafter which the solution was extracted twice with ethyl acetate (50 ml)
16. extractionThe extract was extracted three times with a sodium bicarbonate aqueous solution (50 ml)
17. extractionthe aqueous extract
18. washwas washed with ethyl acetate (50 ml)
19. extractionextracted three times with ethyl acetate (30 ml)
20. washafter which the extract was washed with water
21. customdried
22. distillationAfter the solvent was distilled off
23. additionby adding isopropyl ether

ORD record

ord-f67b970336c94fa7acd27da7055b79d3

Source dataset

uspto-grants-1983_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04385176