4-Methylmorpholine → Cefaclor

HRID 1082332Notes

Reaction equation

HRID 1082332 reaction equation
[K].[C:2]([CH:5]([NH:12]/C(/C)=C\C(OCC)=O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([OH:4])=O.CN1CCOCC1.ClC(OCC)=O.[NH2:34][CH:35]1[C:46](=[O:47])[N:37]2[C:38]([C:43]([OH:45])=[O:44])=[C:39]([Cl:42])[CH2:40][S:41][C@H:36]12>O.C(#N)C.O.C(N(CC)CC)C.C(#N)C.CN(C)C=O>[CH:9]1[CH:10]=[CH:11][C:6]([C@@H:5]([NH2:12])[C:2]([NH:34][C@@H:35]2[C:46](=[O:47])[N:37]3[C:38]([C:43]([OH:45])=[O:44])=[C:39]([Cl:42])[CH2:40][S:41][C@H:36]23)=[O:4])=[CH:7][CH:8]=1

Participants

10

Reactant 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 23620956HCID 23620956, compoundHCID 131719758HCID 131719758, compound

Product 1

HCID 51039CefaclorYield 77.3%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
-40 °C

Procedure

To a mixture of 162 g of ethyl 3-α-carboxybenzylaminocrotonate potassium salt, 450 ml of dimethylformamide and 900 ml of acetonitrile, cooled to -40° C., 1.5 ml of 4-methylmorpholine and 54 ml of ethyl chloroformate are added. The mixture is stirred one hour at -40° C., then a previously cooled solution of triethylamine salt of 7-amino-3-chloro-3-cephem-4-carboxylic acid (corresponding to 99 g of free acid) in 900 ml of a mixture acetonitrile/water 1/1 (v/v) is added thereinto. The solution is kept in the cool for about 3 hours, then it is treated with 630 ml of water and filtered. The filtrate is made acid to pH 1.5 with 6N hydrochloric acid, then the pH is adjusted to 4.5 with triethyl amine. The suspension thus obtained is kept to 0° C. overnight, then it is filtered. The product thus obtained is washed with acetonitrile/water 1/1 (v/v) and dried under vacuum at 35° C. Thus, 120 g of amorphous raw cefaclor are obtained.

Workup

  1. temperaturecool for about 3 hours
  2. filtrationfiltered
  3. customThe suspension thus obtained
  4. waitis kept to 0° C. overnight
  5. filtrationit is filtered
  6. customThe product thus obtained
  7. washis washed with acetonitrile/water 1/1 (v/v)
  8. customdried under vacuum at 35° C

Sources & evidence

ORD record
ord-6ff14aa7c86445708fc5015c99517a4d
Source dataset
uspto-grants-1996_12
Patent number
US05589593

Reaction notes

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