benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate → benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-3-[(1-methylpyrazol-4-yl)methylsulfanyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 992703Notes

Reaction equation

HRID 992703 reaction equation
C[O-].[Na+].[CH3:4][N:5]1[CH:9]=[C:8]([CH2:10][S:11]C(=O)C2C=CC=CC=2)[CH:7]=[N:6]1.[NH2:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:60]/[O:61][C:62]([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)([C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)/[C:27]([NH:29][C@@H:30]2[C:58](=[O:59])[N:32]3[C:33]([C:42]([O:44][CH:45]([C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[O:43])=[C:34](OS(C)(=O)=O)[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1>C1COCC1.CN(C=O)C>[NH2:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:60]/[O:61][C:62]([C:63]2[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=2)([C:75]2[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=2)[C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)/[C:27]([NH:29][C@@H:30]2[C:58](=[O:59])[N:32]3[C:33]([C:42]([O:44][CH:45]([C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)[C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)=[O:43])=[C:34]([S:11][CH2:10][C:8]4[CH:7]=[N:6][N:5]([CH3:4])[CH:9]=4)[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1

Participants

6

Reactant 3

HCID 10748203benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-3-methylsulfonyloxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 10942334Sodium MethoxideHCID 184116014-(Benzoylthiomethyl)-1-methylpyrazole

Product 1

HCID 88158382benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-3-[(1-methylpyrazol-4-yl)methylsulfanyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 47.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-65 °C

Procedure

Under nitrogen atmosphere, 1.35 ml of sodium methoxide (6.5 m mol) was added slowly to a solution of 1.50 g of 1-methyl-4-benzoylthiomethylpyrazole (6.5 m mol) in THF (6 ml) and DMF (18 ml) at 0° C. Stirring was continued for 1 hour. The mixture was cooled to −65° C. with dry ice/ethanol bath, and added to a solution of 4.36 g of diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(trityloxyimino)acetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylate (5 m mol) in a mixture of THF (15 ml) and DMF (25 ml) at the same temperature. After stirring for 1 hour, the reaction was quenched with 10% hydrochloric acid, and the mixture was poured into water-ethyl acetate. The organic layer was separated washed with brine, dried over magnesium sulfate. After filtration, the filtrate was concentrated in vacuo, the residue was purified on silica gel (eluent: dichloromethane-acetone) to afford a diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(trityloxyimino)acetamido]-3-[(1-methylpyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (2.15 g).

Workup

  1. stirringAfter stirring for 1 hour
  2. customthe reaction was quenched with 10% hydrochloric acid
  3. additionthe mixture was poured into water-ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationAfter filtration
  8. concentrationthe filtrate was concentrated in vacuo
  9. customthe residue was purified on silica gel (eluent: dichloromethane-acetone)

Sources & evidence

ORD record
ord-011e35e682e3498a9bd1846b0e2ec230
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

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