Hydrochloric Acid → p-Nitrobenzyl 3-hyroxy-7-phenoxyacetamido-3-cephem-4-carboxylate

HRID 1155432Notes

Reaction equation

HRID 1155432 reaction equation
[O:1]([CH2:8][C:9]1[S:15][CH:14]2[CH:11]([C:12](=[O:33])[N:13]2[C:16](=[C:30]([OH:32])[CH3:31])[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)=[O:18])[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(Cl)(=O)[O:41]C2C=CC=CC=2)C=CC=CC=1.N1CCOCC1.BrBr.Cl>O1CCCC1.N1C=CC=CC=1.C(N(CC)CC)C>[O:1]([CH2:8][C:9]([NH:10][CH:11]1[C:12](=[O:33])[N:13]2[C:16]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=3)=[O:18])=[C:30]([OH:32])[CH2:31][S:15][C@H:14]12)=[O:41])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 24408BromineHCID 99269Phenyl P-phenylphosphonochloridateHCID 70504145p-Nitrobenzyl alpha-[3-phenoxymethyl-7-oxo4-thia-2,6-diazabicyclo[3,2,0]hept-2-en-6-yl]-alpha-(1-hydroxyethylidene)acetate

Product 1

HCID 67616247p-Nitrobenzyl 3-hyroxy-7-phenoxyacetamido-3-cephem-4-carboxylate

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
20 °C

Procedure

To a stirred solution of p-nitrobenzyl α-(3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo(3,2,0)hept-2-en-6-yl)-α-(1-hydroxyethylidene)acetate (9.38 g.) in tetrahydrofuran (120 ml.) under a nitrogen atmosphere at 20° C. was added triethylamine (3.21 ml.) followed by phenyl phenylphosphonochloridate (5.82 g.) After stirring for 2 hours at 20° C., the reaction mixture was cooled to 0° C. and morpholine (4.01 ml.) added. After stirring for 2.5 hours at 0°-5° C., the mixture was cooled to -30° to -35° C. and pyridine (1.62 ml.) added followed by dropwise addition of bromine (1.00 ml.) over a period of 10 minutes. The reaction mixture was stirred at -30° to -35° C. for 20 minutes and 5% hydrochloric acid (144 ml.) added. After stirring at 20° C. overnight the mixture was extracted with dichloromethane and the extracts washed with water and saturated sodium chloride solution, dried with magnesium sulphate and evaporated to dryness. The residue was dissolved in glacial acetic acid (10 ml.) and the resulting solution stirred for approximately 10 minutes to crystallise the product. The crystallisation was completed by addition of isopropanol (120 ml.) over 0.5 hour. The crystals were isolated by filtration, washed with isopropanol and dried in vacuo at 40° C. overnight. The yield of p-nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate acetic acid solvate was 8.29 g. (76%).

Workup

  1. temperaturethe reaction mixture was cooled to 0° C.
  2. stirringAfter stirring for 2.5 hours at 0°-5° C.
  3. temperaturethe mixture was cooled to -30° to -35° C.
  4. stirringThe reaction mixture was stirred at -30° to -35° C. for 20 minutes
  5. stirringAfter stirring at 20° C. overnight the mixture
  6. extractionwas extracted with dichloromethane
  7. washthe extracts washed with water and saturated sodium chloride solution
  8. dry with materialdried with magnesium sulphate
  9. customevaporated to dryness
  10. dissolutionThe residue was dissolved in glacial acetic acid (10 ml.)
  11. stirringthe resulting solution stirred for approximately 10 minutes
  12. customto crystallise the product
  13. customThe crystallisation
  14. additionwas completed by addition of isopropanol (120 ml.) over 0.5 hour
  15. customThe crystals were isolated by filtration
  16. washwashed with isopropanol
  17. customdried in vacuo at 40° C. overnight

Sources & evidence

ORD record
ord-f520c2225c32491c883b0b0329e20a6b
Source dataset
uspto-grants-1981_11
Patent number
US04301280

Reaction notes

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