Ethyl Acetate → HCID 14621685, compound

HRID 1639323Notes

Reaction equation

HRID 1639323 reaction equation
Cl.[NH2:2][CH:3]1[C:24](=[O:25])[N:5]2[C:6]([C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)=[O:13])=[C:7]([CH2:10][Cl:11])[CH2:8][S:9][C@H:4]12.[C:26](OCC)(=[O:28])C.[OH-].[Na+]>O>[Cl:11][CH2:10][C:7]1[CH2:8][S:9][C@@H:4]2[CH:3]([NH:2][CH:26]=[O:28])[C:24](=[O:25])[N:5]2[C:6]=1[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=1)=[O:13]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 14032025HCID 14032025, compound

Product 1

HCID 14621685HCID 14621685, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 15 g (37 mM) of p-methoxybenzyl 7-amino-3-chloromethyl-3-cephem-4-carboxylate hydrochloride, 500 ml of ethyl acetate and 100 ml of water were added. Under cooling with ice, the mixture was adjusted to pH 7.5 with a 1N sodium hydroxide aqueous solution and dissolved. The organic layer was separated, washed with a saturated sodium chloride aqueous solution, and then concentrated under reduced pressure. The oily residue was dissolved in 150 ml of methylene chloride. To this solution, a mixed anhydride solution prepared from 4.8 ml (127 mM) of 99% formic acid and 12 ml (127 mM) of acetic anhydride, was dropwise added under cooling with ice, and the mixture was stirred for 2 hours. The reaction solution was concentrated under reduced pressure. To the residue, 300 ml of ethyl acetate, 300 ml of tetrahydrofuran and 100 ml of water were added, and the mixture was adjusted to pH 7.5 with a 1N sodium hydroxide aqueous solution. The organic layer was separated, and washed with a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 14.5 g (yield: 99%) of p-methoxybenzyl 3-chloromethyl-7-formamido-3-cephem-4-carboxylate.

Workup

  1. temperatureUnder cooling with ice
  2. dissolutiondissolved
  3. customThe organic layer was separated
  4. washwashed with a saturated sodium chloride aqueous solution
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe oily residue was dissolved in 150 ml of methylene chloride
  7. customTo this solution, a mixed anhydride solution prepared from 4.8 ml (127 mM) of 99% formic acid and 12 ml (127 mM) of acetic anhydride
  8. additionwas dropwise added
  9. temperatureunder cooling with ice
  10. concentrationThe reaction solution was concentrated under reduced pressure
  11. additionTo the residue, 300 ml of ethyl acetate, 300 ml of tetrahydrofuran and 100 ml of water were added
  12. customThe organic layer was separated
  13. washwashed with a saturated sodium chloride aqueous solution
  14. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-05cdc2e09d49411d8e1ec2c0c5b72f6a
Source dataset
uspto-grants-1989_11
Patent number
US04883868

Reaction notes

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