1,5-Diazabicyclo(5,4,0)undec-5-ene → 7beta-Phenoxyacetamido-3-methoxy-ceph-2-em-4alpha-carboxylic acid methyl ester

HRID 1155452Notes

Reaction equation

HRID 1155452 reaction equation
N12CCCCC1C=NCCC2.[CH3:12][O:13][C:14](=[O:47])/[C:15](/[N:20]1[CH:23]([S:24]S(C2C=CC(C)=CC=2)(=O)=O)[CH:22]([NH:35][C:36](=[O:45])[CH2:37][O:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:21]1=[O:46])=[C:16](/[O:18][CH3:19])\[CH3:17].COC(=O)/C(/N1C(SS(C2C=CC(C)=CC=2)(=O)=O)C(NC(=O)COC2C=CC=CC=2)C1=O)=C(\OC)/C>O1CCCC1.C(Cl)Cl>[CH3:12][O:13][C:14]([C@@H:15]1[N:20]2[C:21](=[O:46])[C@@H:22]([NH:35][C:36](=[O:45])[CH2:37][O:38][C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[C@H:23]2[S:24][CH:17]=[C:16]1[O:18][CH3:19])=[O:47]

Participants

6

Reactant 3

HCID 3141121,5-Diazabicyclo(5,4,0)undec-5-eneHCID 705570612-[4-(p-Toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl)-3-methoxy-crotonic acid methyl esterHCID 705585572-[4-(p-Toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl)-3-methoxy-isocrotonic acid methyl ester

Product 1

HCID 705574947beta-Phenoxyacetamido-3-methoxy-ceph-2-em-4alpha-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

302 mg (2 mmols) of 1,5-diazabicyclo[5.4.0]undec-5-ene are added to a solution of 534 mg (1 mmol) of a mixture consisting of 2-[4-(p-toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-methoxy-isocrotonic acid methyl ester and 2-[4-(p-toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-methoxy-crotonic acid methyl ester in the ratio of about 4:1, in 20 ml of tetrahydrofurane, whilst stirring. The mixture is then stirred for 40 minutes, diluted with 70 ml of methylene chloride and washed successively with dilute hydrochloric acid, with water, with dilute aqueous sodium bicarbonate solution and again with water. The organic phase is dried over sodium sulphate and concentrated by evaporation in vacuo. The residue is chromatographed on 15 g of acid-washed silica gel using toluene/ethyl acetate, 2:1 followed by 1:1, resulting in the elution of, first, pure 7β-phenoxyacetamido-3-methoxy-ceph-2-em-4α-carboxylic acid methyl ester, IR spectrum (in methylene chloride): characteristic bands at 5.60, 5.70, 5.90 and 8.25μ, followed by pure 7β-phenoxyacetamido-3-methoxy-ceph-3-em-4-carboxylic acid methyl ester, IR spectrum (in methylene chloride): characteristic bands at 5.60, 5.85, 5.90 and 7.10μ, in the form of colourless foams.

Workup

  1. stirringThe mixture is then stirred for 40 minutes
  2. washwashed successively with dilute hydrochloric acid, with water, with dilute aqueous sodium bicarbonate solution and again with water
  3. dry with materialThe organic phase is dried over sodium sulphate
  4. concentrationconcentrated by evaporation in vacuo
  5. customThe residue is chromatographed on 15 g of acid-washed silica gel

Sources & evidence

ORD record
ord-8fc694c3b375471c8b3f91c810036d29
Source dataset
uspto-grants-1981_11
Patent number
US04301278

Reaction notes

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