Ethyl Acetate → 2-Benzhydryloxycarbonyl-7-(3,4-dichlorophenylthio)-acetamido-3-(2-nicotinoylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 2413447Notes

Reaction equation

HRID 2413447 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH2:9][C:10](Cl)=S)[CH:5]=[CH:6][C:7]=1Cl.[C:13]([Cl:18])(=O)[C:14]([Cl:16])=O.N[CH:20]1[C:27](=[O:28])[N:26]2[CH:21]1[S:22][CH2:23][C:24]([C:45]1[S:49][C:48]([NH:50][C:51](=[O:58])[C:52]3[CH:57]=[CH:56][CH:55]=[N:54][CH:53]=3)=[N:47][CH:46]=1)=[C:25]2C(OC(C1C=CC=CC=1)C1C=CC=CC=1)=O.[C:59]([O:62]CC)(=[O:61])[CH3:60]>C(OCC)C.CN(C)C(=O)C>[CH:9]([O:62][C:59]([CH2:60][C:27]([NH:26][C:25]1[N:26]2[CH:21]([S:22][CH2:23][C:24]=1[C:45]1[S:49][C:48]([NH:50][C:51](=[O:58])[C:52]3[CH:57]=[CH:56][CH:55]=[N:54][CH:53]=3)=[N:47][CH:46]=1)[CH:20]([S:49][C:45]1[CH:24]=[CH:23][C:14]([Cl:16])=[C:13]([Cl:18])[CH:46]=1)[C:27]2=[O:28])=[O:28])=[O:61])([C:4]1[CH:3]=[CH:2][CH:7]=[CH:6][CH:5]=1)[C:10]1[CH:55]=[CH:56][CH:57]=[CH:52][CH:51]=1

Participants

7

Reactant 4

HCID 8857Ethyl Acetate2×HCID 65578Oxalyl chlorideHCID 202763043,4-Dichlorophenylthioacetyl chlorideHCID 204304287-Amino-2-benzhydryloxycarbonyl-3-(2-nicotinoylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Product 1

HCID 867399042-Benzhydryloxycarbonyl-7-(3,4-dichlorophenylthio)-acetamido-3-(2-nicotinoylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 31374DimethylacetamideSolvent

Procedure

A solution of 3,4-dichlorophenylthioacetyl chloride (prepared by the action of oxalyl chloride (8.4 cc) on the corresponding acid (3.99 g) in ethyl ether (48 cc), and replacement of the solvent) in ethyl acetate (20 cc) is added, in 10 minutes, to a solution of 7-amino-2-benzhydryloxycarbonyl-3-(2-nicotinoylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (6.43 g) in N,N-dimethylacetamide (25 cc) at 0° C. After 1 hour at 0° C. followed by 40 minutes at a temperature of between 0 ° and 20° C., the reaction mixture is poured into ethyl acetate (250 cc) and this mixture is washed with distilled water (3×100 cc) and then with a saturated sodium chloride solution (100 cc). The organic phase is dried and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residue is filtered on a column of silica (0.02-0.5 mm) (40 g), elution being carried out with a mixture (2 liters) of methylene chloride and methanol (95:5 by volume). The residue obtained after concentrating to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. is crystallised from methylene chloride (20 cc) to give 2-benzhydryloxycarbonyl-7-(3,4-dichlorophenylthio)-acetamido-3-(2-nicotinoylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (2.9 g) in the form of a pale yellow crystalline solid.

Workup

  1. washthis mixture is washed with distilled water (3×100 cc)
  2. customThe organic phase is dried
  3. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
  4. filtrationThe residue is filtered on a column of silica (0.02-0.5 mm) (40 g), elution
  5. customThe residue obtained
  6. concentrationafter concentrating to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C.
  7. customis crystallised from methylene chloride (20 cc)

Sources & evidence

ORD record
ord-33cef257d50f4dd1bcb4a8e379714dc7
Source dataset
uspto-grants-1985_01
Patent number
US04496560

Reaction notes

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