Hydrochloric Acid → HCID 131710593, compound

HRID 1414676Notes

Reaction equation

HRID 1414676 reaction equation
[CH2:1](OC(NC1C(=O)N2C(C(OC(C3C=CC=CC=3)C3C=CC=CC=3)=O)C(N=C=O)=CS[C@H]12)=O)[C:2]1C=CC=C[CH:3]=1.C(C(CC)(C([O-])=O)C([O-])=O)C.[Na+].[Na+].[ClH:53].C(OC(NC1C(=O)N2C(C(OC(C3C=CC=CC=3)C3C=CC=CC=3)=O)=C(NC(=O)C(C(OCC)=O)C(OCC)=O)CS[C@H]12)=O)C1C=CC=CC=1.Cl[C:105]1[CH:106]=[C:107]([CH2:111][C:112]([NH:114][CH:115]2[C:132](=[O:133])[N:117]3[CH:118]([C:125]([O:127][C:128]([CH3:131])([CH3:130])[CH3:129])=[O:126])[C:119]([N:122]=[C:123]=[O:124])=[CH:120][S:121][C@H:116]23)=[O:113])[CH:108]=[CH:109][CH:110]=1.C([Mg]Br)(C)C>O1CCCC1>[Cl:53][C:108]1[CH:109]=[CH:110][CH:105]=[CH:106][C:107]=1[CH2:111][C:112]([NH:114][CH:115]1[C:132](=[O:133])[N:117]2[C:118]([C:125]([O:127][C:128]([CH3:131])([CH3:130])[CH3:129])=[O:126])=[C:119]([NH:122][C:123](=[O:124])[CH:2]([CH3:3])[CH3:1])[CH2:120][S:121][C@H:116]12)=[O:113]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 22037854HCID 22037854, compoundHCID 70636377HCID 70636377, compoundHCID 88820492HCID 88820492, compoundHCID 131710594HCID 131710594, compoundHCID 178418365HCID 178418365, compound

Product 1

HCID 131710593HCID 131710593, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

As in the case of the aforedescribed reaction of amines with the 3-isocyanato-2-cephems, the reaction of such isocyanates with carbanionic reagents is accompanied by the rearrangement of the double bond in the cephem ring. Thus, benzhydryl 7-benzyloxycarbonylamino-3-isocyanato-2-cephem-4-carboxylate reacts with 1.1 equivalents of sodium diethylmalonate in tetrahydrofuran at -20° C. over a 5 minute period, to provide after hydrolysis with about 3 equivalents of 1N.HCl, benzhydryl 7 -benzyloxycarbonylamino-3-di(ethoxycarbonyl)acetamido-3-cephem-4-carboxylate. Likewise tert-butyl 7-(3-chlorophenylacetamido)-3-isocyanato-2-cephem-4carboxylate reacts with about 1.1 equivalents of isopropylmagnesium bromide in tetrahydrofuran at about --70° C. over a 30 minute period to give, upon acid hydrolysis, tert-butyl 7-(2-chlorophenylacetamido)-3-(2-methyl-propionamido)-3-cephem-4-carboxylate. The reaction of methyllithium with 4-methoxybenzyl 7-acetamido-3-isocyanato-3-cephem-4-carboxylate under similar conditions yields 4-methoxybenzyl 7-acetamido-3-acetamido-3-cephem-4-carboxylate.

Workup

  1. customto provide
  2. customafter hydrolysis with about 3 equivalents of 1N

Sources & evidence

ORD record
ord-b0decf1968fc4eafb72158a60324b79b
Source dataset
uspto-grants-1977_01
Patent number
US04001226

Reaction notes

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