Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

Temperature

40 °C

The solution of Vilsmeier reagent was prepared from dry N,N-dimethylformamide (0.48 g), phosphoryl chloride (1.0 g), ethyl acetate (4 ml) and tetrahydrofuran (15 ml) in a usual manner. To the solution was added 2-(2-cyclopenten-1-yl)oxyimino-2-[2-(2,2,2-trifluoroacetamido)thiazol-4-yl]acetic acid (syn isomer) (1.9 g) under ice cooling and the resulting solution was stirred for 30 minutes (Solution A). A mixture of N-[7-amino-3-cephem-3-ylmethyl]pyridinium-4-carboxylate dihydrochloride (2.0 g), trimethylsilylacetamide (5.7 g) and tetrahydrofuran (40 ml) was warmed to 40° C. and stirred to give a homogeneous solution, which was cooled to -25° C. and then thereto was added Solution A. The resulting mixture was stirred for 30 minutes around -10° C. To the reaction mixture containing N-[7-[2-(2-cyclopenten-1-yl)oxyimino-2-{2-(2,2,2-trifluoroacetamido)thiazol-4-yl}acetamido]-3-cephem-3-ylmethyl]pyridinium-4-carboxylate (syn isomer) were added ethyl acetate (50 ml) and water (100 ml). The ethyl acetate layer was separated and extracted with a saturated aqueous solution of sodium bicarbonate (50 ml). The extract and the remaining aqueous layer was combined, adjusted to pH 6.0 with 4N aqueous solution of sodium hydroxide and then thereto was added sodium acetate (7.5 g). The mixture was stirred for 41 hours at room temperature, adjusted to pH 2.0 with 10% hydrochloric acid, and then filtered. The filtrate was subjected to column chromatography (non-ion adsorption resin, Diaion HP20 prepared by Mitsubishi Chemical Industries) (60 ml) and the column was washed with water and then eluted with 10% isopropyl alcohol and 30% methanol. The eluates containing the object compound were collected, evaporated and lyophilized. The obtained powder was dried over phosphorus pentoxide under reduced pressure to give N-[7-{2-(2-cyclopenten-1-yl)oxyimino-2-(2-amino-thiazol-4-yl)acetamido}-3-cephem-3-ylmethyl]pyridinium-4-carboxylate (syn isomer) (0.3 g). mp. 171° to 180° C. (dec.).

1. customto give a homogeneous solution, which
2. temperaturewas cooled to -25° C.
3. stirringThe resulting mixture was stirred for 30 minutes around -10° C
4. customThe ethyl acetate layer was separated
5. extractionextracted with a saturated aqueous solution of sodium bicarbonate (50 ml)
6. extractionThe extract
7. additionwas added sodium acetate (7.5 g)
8. stirringThe mixture was stirred for 41 hours at room temperature
9. filtrationfiltered
10. customThe filtrate was subjected to column chromatography (non-ion adsorption resin, Diaion HP20 prepared by Mitsubishi Chemical Industries) (60 ml)
11. washthe column was washed with water
12. washeluted with 10% isopropyl alcohol and 30% methanol
13. additionThe eluates containing the object compound
14. customwere collected
15. customevaporated
16. dry with materialThe obtained powder was dried over phosphorus pentoxide under reduced pressure

ORD record

ord-f7118b5424a345ea83ed4b4bd8bbce99

Source dataset

uspto-grants-1985_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04529802