Methanesulfonyl chloride → (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-2-yl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 973876Notes

Reaction equation

HRID 973876 reaction equation
C1(C([NH:20][C:21]2[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)/[C:27]([O-:29])=O)[N:25]=2)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Na+].CS(Cl)(=O)=O.[NH2:57][C@@H:58]1[C:88](=[O:89])[N:60]2[C:61]([C:72]([O:74]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:73])=[C:62]([CH2:65][CH:66]3[O:70][C:69](=[O:71])[CH:68]=[CH:67]3)[CH2:63][S:64][C@H:59]12>CN(C=O)C>[NH2:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[OH:31])/[C:27]([NH:57][C@@H:58]2[C:88](=[O:89])[N:60]3[C:61]([C:72]([OH:74])=[O:73])=[C:62]([CH2:65][CH:66]4[O:70][C:69](=[O:71])[CH:68]=[CH:67]4)[CH2:63][S:64][C@H:59]23)=[O:29])[N:25]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 23714200sodium (2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetateHCID 67923925diphenylmethyl 7beta-amino-3-[(5RS)-2,5-dihydro-2-oxofuran-5-ylmethyl]ceph-3-em-4-carboxylate

Product 1

HCID 88512331(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-[(5-oxo-2H-furan-2-yl)methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 82.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium 2-(2-triphenylmethylaminothiazol-4-yl)-2-Z-triphenylmethoxyiminoacetate (1.33 g) in DMF (5 mls) was activated with methanesulphonyl chloride (0.148 mls) as described in example 7(a). Treatment with diphenylmethyl 7β-amino-3-[(5RS)-2,5-dihydro-2-oxofuran-5-ylmethyl]ceph-3-em-4-carboxylate (0.737 g) in DMF (5 mls), work up and purification by repeated flash, silica gel chromatography afforded major isomer of the title compound, (0.614 g, 35%), νmax 3380(w), 1785, 1770 (shoulder), 1755 (shoulder), 1725, 1685, 1510 and 1370cm-1 ; δH (CDCl3) 2.25 (1H, dd, J 9.9, 13.7Hz), 3.16 (1H, dd, J 2.9, 13.7Hz), 3.49 and 3.53 (2H, ABq, J 18.7Hz), 5.03 (1H, d, J 4.9Hz), 5.22 (1H, J 7.9Hz), 6.05 (1H, dd, J 1.9, 5.7Hz), 6.14 (1H, dd, J 4.9, 9.1Hz), 6.45 (1H, s), 6.76 (1H, broad s, exch.), 6.90 (1H, s), 7.07 (1H, d, J 9.1Hz, exch.), 7.19 (1H, dd, J 1.4, 5.7Hz) and 7.24 to 7.50 (40H, m); [mass spectrum: +ve ion (NOBA, Na+) MNa+ 1138]. The minor isomer was not progressed.

Workup

  1. custompurification by repeated flash, silica gel chromatography

Sources & evidence

ORD record
ord-042f3225dac94fd180aa07cc8b6ba721
Source dataset
uspto-grants-1991_11
Patent number
US05064649

Reaction notes

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