Ethyl Acetate → 3-(1-Pyridinio)methyl-3-cephem-4-carboxylate

1-[(7β-Amino-4-carboxy-3-cephem-3-yl)methyl]pyridinium chloride hydrochloride (960 mg) was dissolved in a solution of N-trimethylsilylacetamide (1.5 g) and bis(trimethylsilyl)acetamide (2.8 ml) in tetrahydrofuran (10 ml). To this solution was added the activated acid solution, which was prepared from 2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (500 mg) according to a similar manner to that described in Example 1, at -20° C. The mixture was stirred at -20° C. to -10° C. for 40 minutes. The mixture was poured into ethyl acetate (250 ml). The precipitate was collected and suspended in methanol (20 ml). To the suspension was added concentrated hydrochloric acid (0.62 ml) and the mixture was warmed at 30° to 35° C. for 2 hours. The mixture was poured into ice-water (50 ml), adjusted to pH 2.5 with saturated aqueous solution of sodium bicarbonate, and washed with ethyl acetate. The aqueous solution was subjected to column chromatography on a non-ionic adsorption resin "Diaion HP-20" (30 ml). After the column was washed with water (300 ml), 1% isopropyl alcohol (60 ml), and 3% isopropyl alcohol (60 ml) successively, the elution was carried out with 5% isopropyl alcohol (250 ml) and 10% isopropyl alcohol (150 ml) successively. The fractions containing the object compound were collected, combined, concentrated in vacuo to about 100 ml and lyophilized to give 7β-2-(2-aminothiazol-4-yl)-2-(cyclopropyloxyimino)acetamido]-3-(1-pyridinio)methyl-3-cephem-4-carboxylate (syn isomer) (553 mg).

1. additionTo this solution was added the activated acid solution, which
2. customdescribed in Example 1, at -20° C
3. customThe precipitate was collected
4. additionTo the suspension was added concentrated hydrochloric acid (0.62 ml)
5. temperaturethe mixture was warmed at 30° to 35° C. for 2 hours
6. additionThe mixture was poured into ice-water (50 ml)
7. washwashed with ethyl acetate
8. washAfter the column was washed with water (300 ml), 1% isopropyl alcohol (60 ml), and 3% isopropyl alcohol (60 ml) successively
9. washthe elution
10. additionThe fractions containing the object compound
11. customwere collected
12. concentrationconcentrated in vacuo to about 100 ml

ORD record

ord-71f09e03061e47a781c62ef613933b4a

Source dataset

uspto-grants-1990_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04973699