Hydrochloric Acid → benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-[(Z)-2-phenylvinylthiomethyl]-3-cephem-4-carboxylate

HRID 1731693Notes

Reaction equation

HRID 1731693 reaction equation
[C:1]([S:4]/[CH:5]=[CH:6]\[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)(=O)[CH3:2].C[O-].[Na+].[NH2:16][C:17]1[S:21][N:20]=[C:19]([C:22](=[N:53][O:54][CH2:55][CH:56]=[CH2:57])[C:23]([NH:25][CH:26]2[C:51](=[O:52])[N:28]3[C:29]([C:35]([O:37][CH:38]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[O:36])=C(CCl)[CH2:31][S:32][C@H:27]23)=[O:24])[N:18]=1.Cl.[Cl-].[Na+]>O1CCCC1.CO.C(OCC)(=O)C>[NH2:16][C:17]1[S:21][N:20]=[C:19]([C:22](=[N:53][O:54][CH2:55][CH:56]=[CH2:57])[C:23]([NH:25][CH:26]2[C:51](=[O:52])[N:28]3[C:29]([C:35]([O:37][CH:38]([C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)[C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)=[O:36])=[C:2]([CH2:1][S:4]/[CH:5]=[CH:6]\[C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)[CH2:31][S:32][C@H:27]23)=[O:24])[N:18]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 10559232(Z)-2-acetylthiovinylbenzeneHCID 10942334Sodium MethoxideHCID 131714957Benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate

Product 1

HCID 131714954benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-[(Z)-2-phenylvinylthiomethyl]-3-cephem-4-carboxylateYield 46.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (Z)-2-acetylthiovinylbenzene (500 mg) in tetrahydrofuran (5 ml) was dropwise added a solution of sodium methoxide (13.9 mg) in a mixture of methanol (358 mg) and tetrahydrofuran (2 ml) under ice-cooling. The mixture was stirred for 30 minutes under the same condition. The resulting solution was dropwise added to a solution of benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate (syn isomer) (1.46 g) in tetrahydrofuran (20 ml) at -30° C. The mixture was stirred at the same temperature for 30 minutes. The reaction temperature was gradually raised to 0° C. 1N Hydrochloric acid (3 ml) was added to the reaction mixture at 0° C. Ethyl acetate and a saturated aqueous solution of sodium chloride were added to the mixture. The separated organic layer was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated in diisopropyl ether to give a solid, which was subjected to column chromatography on silica gel (50 g) and eluted with a mixture of chloroform and methanol (100:1, V/V). The fractions containing the object compound were combined and concentrated in vacuo. The residue was triturated in diisopropyl ether to give benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-allyloxyiminoacetamido]-3-[(Z)-2-phenylvinylthiomethyl]-3-cephem-4-carboxylate (syn isomer) (790 mg).

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred at the same temperature for 30 minutes
  3. washThe separated organic layer was washed with a saturated aqueous solution of sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated in diisopropyl ether
  7. customto give a solid, which
  8. washeluted with a mixture of chloroform and methanol (100:1, V/V)
  9. additionThe fractions containing the object compound
  10. concentrationconcentrated in vacuo
  11. customThe residue was triturated in diisopropyl ether

Sources & evidence

ORD record
ord-f9a1a041672946c8af3938e1686a2485
Source dataset
uspto-grants-1986_11
Patent number
US04622318

Reaction notes

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