Hydrochloric Acid → Diphenylmethyl 7beta-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate

Diphenylmethyl 7β-formamido-3-[(1-tritylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (121.7 g) was suspended in methanol (1.46 l), concentrated hydrochloric acid (94.8 ml) was added thereto below 25° C. The reaction mixture was stirred at the room temperature for 3 hours, and then concentrated hydrochloric acid (4.0 ml) was added. After the reaction mixture was stirred at the same temperature for one hour, insoluble precipitate was filtered off below 10° C. The filtrate was poured into a mixture of ethyl acetate (4.5 l) and water (4 l). The aqueous layer was adjusted at pH 4.0 with 30% aqueous sodium hydroxide solution and then was adjusted at pH 6.9 with 2N-potassium hydroxide. The organic layer was separated, washed with brine (4 l), dried over magnesium sulfate, and evaporated until the volume amounted to 700 ml. IPE (100 ml) was added to the suspension gradually below 10° C., and was left below 10° C. for 12 hours. The precipitate was filtered and dried under reduced pressure to give diphenylmethyl 7β-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (62.4 g) as powder.

1. custombelow 25° C
2. stirringAfter the reaction mixture was stirred at the same temperature for one hour
3. filtrationinsoluble precipitate was filtered off below 10° C
4. additionThe filtrate was poured into a mixture of ethyl acetate (4.5 l) and water (4 l)
5. customThe organic layer was separated
6. washwashed with brine (4 l)
7. dry with materialdried over magnesium sulfate
8. customevaporated until the volume
9. additionIPE (100 ml) was added to the suspension gradually below 10° C.
10. waitwas left below 10° C. for 12 hours
11. filtrationThe precipitate was filtered
12. customdried under reduced pressure

ORD record

ord-10eb856692a44ce6b6a939cf69a4a69f

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06468995B1