Acetyl chloride → 3-Acetoxymethyl-7-amino-3cephem-4-carboxylic acid

HRID 2057606Notes

Reaction equation

HRID 2057606 reaction equation
[CH3:1][C:2]([O:4][CH2:5][C:6]1[CH2:25][S:24][C@@H:9]2[C@H:10]([NH:13]C(CCC[C@@H](N)C(O)=O)=O)[C:11](=[O:12])[N:8]2[C:7]=1[C:26]([OH:28])=[O:27])=[O:3].[Na].C(N(CC)C1C=CC=CC=1)C.C(Cl)(=O)C>O1CCCC1>[NH2:13][CH:10]1[C:11](=[O:12])[N:8]2[C:7]([C:26]([OH:28])=[O:27])=[C:6]([CH2:5][O:4][C:2](=[O:3])[CH3:1])[CH2:25][S:24][C@H:9]12

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 7061N,N-DiethylanilineHCID 65536Cephalosporin CHCID 5360545Sodium

Product 1

HCID 113463103-Acetoxymethyl-7-amino-3cephem-4-carboxylic acidYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-35 °C

Procedure

Cephalosporin C, sodium salt, dihydrate, 4.8 gm (10 mmol), was suspended in 80 ml of tetrahydrofuran (dried over 5A molecular sieves). Diethyl aniline (dried over KOH), 7.4 gm (8.0 ml, 50 mmol), and acetyl chloride, 4.7 gm (4.3 ml, 60 mmol), were added. The mixture was stirred in a water bath at about 30° to 40° C. for 1 hour and then at room temperature for about 2.5 hours. Filtration removed 5.7 gm of undissolved material. The reaction solution was cooled in an ice-alcohol bath before addition to a solution of the triphenyl phosphitechlorine complex prepared as in Paragraph A above, but using tetrahydrofuran as a solvent instead methylene chloride. After mixing the two solutions, a solution of diethylaniline, 3.3 gm (22 mmol) in 20 ml of dry tetrahydrofuran, was added dropwise over a period of 10 minutes. The reaction mixture was stirred in the cold for 2 hours, cooled further to about -35° C., and then treated with 16 ml of propylene glycol. A stream of dry hydrogen chloride was passed through the reaction for about 15 seconds. The reaction solution was refrigerated overnight. Workup as described in Paragraph A immediately hereinabove yielded 1.2 gm (45%) of 7-ACA.

Workup

  1. waitat room temperature for about 2.5 hours
  2. filtrationFiltration
  3. customremoved 5.7 gm of undissolved material
  4. temperatureThe reaction solution was cooled in an ice-alcohol bath before addition to a solution of the triphenyl phosphitechlorine complex prepared as in Paragraph A above, but
  5. additionAfter mixing the two solutions
  6. additiona solution of diethylaniline, 3.3 gm (22 mmol) in 20 ml of dry tetrahydrofuran, was added dropwise over a period of 10 minutes
  7. stirringThe reaction mixture was stirred in the cold for 2 hours
  8. additiontreated with 16 ml of propylene glycol
  9. customA stream of dry hydrogen chloride was passed through the reaction for about 15 seconds
  10. waitThe reaction solution was refrigerated overnight

Sources & evidence

ORD record
ord-cddc1d8533a94c0b840f9d0c42096053
Source dataset
uspto-grants-1980_07
Patent number
US04211702

Reaction notes

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