Acetic Acid → Diphenylmethyl (6R,7R)-8-oxo-7-((phenylacetyl)amino)-3-((4-(pyridin-4-yl)-1,3-thiazol-2-yl)thio)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylate

HRID 1071315Notes

Reaction equation

HRID 1071315 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:8]=[C:9]([SH:12])[S:10][CH:11]=2)=[CH:3][CH:2]=1.[Na].[C:14]1([CH2:20][C:21]([NH:23][C@@H:24]2[C:52](=[O:53])[N:26]3[C:27]([C:36]([O:38][CH:39]([C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)[C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[O:37])=[C:28](OS(C)(=O)=O)[CH2:29][S:30][C@H:25]23)=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(O)(=O)C>O1CCCC1.O.CO>[C:14]1([CH2:20][C:21]([NH:23][C@@H:24]2[C:52](=[O:53])[N:26]3[C:27]([C:36]([O:38][CH:39]([C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=4)[C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)=[O:37])=[C:28]([S:12][C:9]4[S:10][CH:11]=[C:7]([C:4]5[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=5)[N:8]=4)[CH2:29][S:30][C@H:25]23)=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5360545SodiumHCID 11050121diphenylmethyl (6R,7R)-3-[(methylsulfonyl)oxy]-8-oxo-7-[(phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 178527846HCID 178527846, compound

Product 1

HCID 68808181Diphenylmethyl (6R,7R)-8-oxo-7-((phenylacetyl)amino)-3-((4-(pyridin-4-yl)-1,3-thiazol-2-yl)thio)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylateYield 76%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

4-(4-Pyridyl)-1,3-thiazole-2-thiol (225 g, 1.16 mol) was suspended in tetrahydrofuran (1.5 L) and 28% sodium methylatemethanol solution (235 g, 1.22 mol) was added dropwise at 25° C. over 10 min. The mixture was stirred for 1 hr. The reaction mixture was ice-cooled and benzhydryl 7β-[(phenylacetyl)amino]-3-[(methylsulfonyl)oxy]-3-cephem-4-carboxylate (479 g, 0.83 mol) dissolved in tetrahydrofuran (3.5 L) was added dropwise over 30 min. The mixture was stirred at 0° C. for 1 hr and a mixture of acetic acid (50 mL), methanol (5 L) and water (7 L) was added dropwise over 30 min. The mixture was stirred at 0° C. for 2 hr, and the precipitated crystals were collected by filtration. The obtained crystals were washed with methanol (1 L×2) and dried in vacuo to give the title compound (438 g, 0.63 mol). yield: 76%.

Workup

  1. temperaturecooled
  2. additionwas added dropwise over 30 min
  3. stirringThe mixture was stirred at 0° C. for 1 hr
  4. additionwas added dropwise over 30 min
  5. stirringThe mixture was stirred at 0° C. for 2 hr
  6. filtrationthe precipitated crystals were collected by filtration
  7. washThe obtained crystals were washed with methanol (1 L×2)
  8. customdried in vacuo

Sources & evidence

ORD record
ord-6436e90aa7c0461c8ed225d658544d81
Source dataset
uspto-grants-2005_06
Patent number
US06906055B2

Reaction notes

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