Cephalothin → HCID 70636083, compound

HRID 596830Notes

Reaction equation

HRID 596830 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][C:10]1([O:27][CH3:28])[C:25](=[O:26])[N:12]2[C:13]([C:22]([OH:24])=[O:23])=[C:14]([CH2:17][O:18][C:19](=[O:21])[CH3:20])[CH2:15][S:16][C@H:11]12)=[O:8].CC(OCC1CS[C@@H]2[C@H](NC(CC3SC=CC=3)=O)C(=O)N2C=1C(O)=O)=O.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][C:10]1([O:27][CH3:28])[C:25](=[O:26])[N:12]2[CH:13]([C:22]([OH:24])=[O:23])[C:14]([CH2:17][O:18][C:19](=[O:21])[CH3:20])=[CH:15][S:16][C@H:11]12)=[O:8]

Participants

5

Reactant 3

HCID 6024CephalothinHCID 7918Acetic AnhydrideHCID 64521823-[(Acetyloxy)methyl]-7-{[1-hydroxy-2-(thiophen-2-yl)ethylidene]amino}-7-methoxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Product 1

HCID 70636083HCID 70636083, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a cooled (0°), stirred solution of 7.75 g. of 7-(2-thienylacetamido)-7-methoxy-3-acetoxymethyl-3-cephem-4-carboxylic acid [prepared from cephalothin in accordance with procedures described by G. A. Koppel and R. E. Koehler, J. Amer. Chem. Soc., 95, 2403 (1973)] in 46 ml. of dry pyridine was added 5.02 ml. of acetic anhydride. The reaction mixture was allowed to stir with cooling for 2 hours, after which time the mixture was evaporated in vacuo to near dryness. The residue was dissolved in ethyl acetate, and the resulting solution was extracted 3 times with aqueous sodium bicarbonate. The aqueous extracts were combined, layered with ethyl acetate, and acidified with cold 1N.HCl. The organic layer was separated, washed with brine and dried over anhydrous sodium sulfate. Evaporation in vacuo to dryness provided 5.29 g. (68.2 percent) of the title product as a brown froth. Thin layer chromatography of the methyl ester derived from diazomethane exhibited a single spot. For identification purposes a small portion of the product acid was also converted to the corresponding benzhydryl ester using diphenyldiazomethane. Chromatography on a small silica gel column provided pure benzhydryl 7-(2-thienylacetamido)-7-methoxy-3-acetoxymethyl-2-cephem-4-carboxylate: ir (CHCl3) 1780 cm-1 (β-lactam); nmr (CDCl3) δ1.92 (s, 3, OAc), 3.42 (s, 3, OCH3), 3.85 (s, 2, side chain CH2), 4.55 (s, 2, --CH2OAc), 5.01 (m, 1, C4 --H), 5.35 (s, 1, C6 --H) and 6.35 (m, 6, CH2).

Workup

  1. temperatureTo a cooled (0°)
  2. stirringto stir
  3. temperaturewith cooling for 2 hours
  4. customafter which time the mixture was evaporated in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. extractionthe resulting solution was extracted 3 times with aqueous sodium bicarbonate
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. customEvaporation in vacuo to dryness
  11. customprovided 5.29 g

Sources & evidence

ORD record
ord-6df12f171afe43a7bdfded9ec208a26b
Source dataset
uspto-grants-1977_03
Patent number
US04012380

Reaction notes

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