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 28406Notes

Reaction equation

HRID 28406 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.C[O-].[Na+].CO.[C:18]1([CH2:24][C:25]([NH:27][C@@H:28]2[C:56](=[O:57])[N:30]3[C:31]([C:40]([O:42][CH:43]([C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[O:41])=[C:32](OS(C)(=O)=O)[CH2:33][S:34][C@H:29]23)=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O)(=O)C>O1CCCC1.O.CO>[C:18]1([CH2:24][C:25]([NH:27][C@@H:28]2[C:56](=[O:57])[N:30]3[C:31]([C:40]([O:42][CH:43]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)[C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=4)=[O:41])=[C:32]([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)[CH2:33][S:34][C@H:29]23)=[O:26])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 11050121diphenylmethyl (6R,7R)-3-[(methylsulfonyl)oxy]-8-oxo-7-[(phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 23694274Sodium methanolate methanolHCID 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 methylate-methanol 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-ff01591c0b7e46e5b78fb03e7ff3b13f
Source dataset
uspto-grants-2008_09
Patent number
US07419973B2

Reaction notes

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