Pyridine → Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylate

Temperature

20 °C

To a slurry of PCl5 (8.3 g, 40 mmoles) in CH2Cl2 (100 mL) was added pyridine (3.2 g, 40 mmoles) and the mixture was stirred for 20 minutes at 20° C. To the mixture was added benzhydryl 3-hydroxymethyl-7-phenylacetamido-3-cephem-4-carboxylate prepared in Preparation No. 3 (5.1 g, 10 mmoles) with stirring at -40° C., in one portion. The mixture was stirred at -10° C. for 15 minutes and allowed to stand at -10° C. to -15° C. for 7 hours. To the cooled solution (-20° C.) was added propane-1,3-diol (10 mL) and the mixture was allowed to stand at -20° C. for 16 hours and then at room temperature for 20 minutes with stirring. The resulting solution was washed with ice-water (2×20 mL) and saturated aqueous NaCl (10 mL), dried over MgSO4 and concentrated in vacuo. The gummy residue (12 g) was dissolved in a mixture of CHCl3 and n-hexane (2:1), and subjected to chromatography using a silica gel column (200 g) and the same solvent as eluant. Fractions containing the title compound were evaporated in vacuo and the residue triturated with n-hexane to give the title product (2.1 g, 51%), melting at >110° C. (dec.).

1. customprepared in Preparation No
2. stirringThe mixture was stirred at -10° C. for 15 minutes
3. waitto stand at -10° C. to -15° C. for 7 hours
4. waitto stand at -20° C. for 16 hours
5. stirringat room temperature for 20 minutes with stirring
6. washThe resulting solution was washed with ice-water (2×20 mL) and saturated aqueous NaCl (10 mL)
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. dissolutionThe gummy residue (12 g) was dissolved in a mixture of CHCl3 and n-hexane (2:1)
10. additionFractions containing the title compound
11. customwere evaporated in vacuo
12. customthe residue triturated with n-hexane

ORD record

ord-94d01a2cc41b405e9fa49a3b57a94f96

Source dataset

uspto-grants-1985_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04500526