Pyridine → 7-Aminodeacetoxycephalosporanic acid

Dry pyridine (2.0 ml. 2.4 × 10-2 mole) was added dropwise over 1 minute to a stirred suspension of phosphorus pentachloride (5.12g, 2.4 × 10-2 mole) in methylene chloride (50 ml.) and the mixture stirred at 25°-30° for 25 minutes and then cooled to -10°. The polymer ester of (6R,7R)-3-methyl-7-phenylacetamidoceph-3-em-4-carboxylic acid (10.5g, containing 1.04 × 10-2 mole cephalosporin moiety) prepared as in example 8, was then added and washed in with methylene chloride (30 ml.). The slurry was stirred at room temperature for 90 minutes, cooled to -10° and treated with methanol (5.0 ml) such that the temperature did not rise above 0°. After stirring for 10 minutes further methanol (8 ml) was added and the mixture was stirred at room temperature for 30 minutes. The mixture was then filtered directly with no water treatment and the polymer was washed with methylene chloride (4 × 50 ml), and pulled dry. The damp polymer was slurried directly in 98% formic acid (25 ml) and the mixture poured into a glass column. The polymer was eluted with a mixture of methylene chloride/formic acid (140 ml, 1:1) containing toluene-4-sulphonic acid (4.2g). The combined eluate was evaporated and the residue worked-up as in example 21 to afford the title acid (0.815g, 36.8%) as an off-white crystalline solid. The IR and NMR spectra and t.l.c. of the product were identical with those of an authentic sample. [a]D20 150° (c. 0.5 in 0.2M, pH 7.0 phosphate buffer).

1. temperaturecooled to -10°
2. additionwas then added
3. washwashed in with methylene chloride (30 ml.)
4. stirringThe slurry was stirred at room temperature for 90 minutes
5. temperaturecooled to -10°
6. additiontreated with methanol (5.0 ml) such that the temperature
7. customdid not rise above 0°
8. stirringAfter stirring for 10 minutes further methanol (8 ml)
9. additionwas added
10. stirringthe mixture was stirred at room temperature for 30 minutes
11. filtrationThe mixture was then filtered directly with no water treatment
12. washthe polymer was washed with methylene chloride (4 × 50 ml)
13. custompulled dry
14. additionthe mixture poured into a glass column
15. washThe polymer was eluted with a mixture of methylene chloride/formic acid (140 ml, 1:1)
16. additioncontaining toluene-4-sulphonic acid (4.2g)
17. customThe combined eluate was evaporated
18. customto afford the title acid (0.815g, 36.8%) as an off-white crystalline solid

ORD 기록

ord-41bf745fe90d4534ab46f6bef0d15fb9

출처 데이터셋

uspto-grants-1978_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US04067858