1,3-Bis(trimethylsilyl)urea → 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[(Z)-2-phenylvinylthio]-3-cephem-4-carboxylic acid

HRID 704271Notes

Reaction equation

HRID 704271 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:28][O:29][CH2:30][CH3:31])[C:8]([NH:10][CH:11]2[C:26](=[O:27])[N:13]3[C:14]([C:23]([OH:25])=[O:24])=[C:15](OS(C)(=O)=O)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1.C[Si](NC(N[Si](C)(C)C)=O)(C)C.C([S:47]/[CH:48]=[CH:49]\[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)(=O)C.C[O-].[Na+].C(=O)(O)[O-].[Na+]>O1CCCC1.O>[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:28][O:29][CH2:30][CH3:31])[C:8]([NH:10][CH:11]2[C:26](=[O:27])[N:13]3[C:14]([C:23]([OH:25])=[O:24])=[C:15]([S:47]/[CH:48]=[CH:49]\[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

8

Reactant 5

HCID 875621,3-Bis(trimethylsilyl)ureaHCID 516892Sodium BicarbonateHCID 10559232(Z)-2-acetylthiovinylbenzeneHCID 10942334Sodium MethoxideHCID 1317161577-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-mesyloxy-3-cephem-4-carboxylic acid

Product 1

HCID 1317161567-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[(Z)-2-phenylvinylthio]-3-cephem-4-carboxylic acidYield 50.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-mesyloxy-3-cephem-4-carboxylic acid (syn isomer)(1 g) in tetrahydrofuran (30 ml) was added bis(trimethylsilyl)urea (444 mg) at ambient temperature. The mixture was stirred at 30°-35° C. for 30 minutes to give a clear solution. On the other hand, to a solution of (Z)-2-acetylthiovinylbenzene (780 mg) in tetrahydrofuran (6 ml) was added sodium methoxide (240 mg) at 0° C. The mixture was stirred for 30 minutes. This solution was added to the above-mentioned clear solution. The mixture was stirred for 2 hours at -20°~30° C. The mixture was poured into water (300 ml), and then the mixture was neutralized with sodium bicarbonate and washed with ethyl acetate. After stirring, the aqueous layer was separated. The aqueous solution was adjusted to pH 2.5 with 1N hydrochloric acid. To this solution was added ethyl acetate (200 ml). The organic layer was separated, dried over magnesium sulfate and concentrated in vacuo to give a solid. The solid was triturated with diisopropyl ether to give 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[(Z)-2-phenylvinylthio]-3-cephem-4-carboxylic acid (syn isomer)(550 mg).

Workup

  1. customto give a clear solution
  2. stirringThe mixture was stirred for 30 minutes
  3. additionThis solution was added to the above-mentioned clear solution
  4. stirringThe mixture was stirred for 2 hours at -20°~30° C
  5. washwashed with ethyl acetate
  6. stirringAfter stirring
  7. customthe aqueous layer was separated
  8. additionTo this solution was added ethyl acetate (200 ml)
  9. customThe organic layer was separated
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. customto give a solid
  13. customThe solid was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-2a4c22d01dca461e84932311818b7665
Source dataset
uspto-grants-1991_01
Patent number
US04985555

Reaction notes

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