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

HRID 973875Notes

Reaction equation

HRID 973875 reaction equation
C([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:30]/[O:31]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)/[C:27]([O-:29])=O)[N:25]=1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Na+].CS(Cl)(=O)=O.[NH2:57][C@@H:58]1[C:91](=[O:92])[N:60]2[C:61]([C:75]([O:77]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:76])=[C:62](/[CH:65]=[C:66]3/[C:67]([O:73][CH3:74])=[C:68]([CH3:72])[C:69](=[O:71])[O:70]/3)[CH2:63][S:64][C@H:59]12>CN(C=O)C.C(OCC)(=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:91](=[O:92])[N:60]3[C:61]([C:75]([OH:77])=[O:76])=[C:62](/[CH:65]=[C:66]4/[C:67]([O:73][CH3:74])=[C:68]([CH3:72])[C:69](=[O:71])[O:70]/4)[CH2:63][S:64][C@H:59]23)=[O:29])[N:25]=1

Participants

6

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 23714200sodium (2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetateHCID 67923960diphenylmethyl 7beta-amino-3-(Z-2,5-dihydro-4-methoxy-3-methyl-2-oxofuran-5-ylidenemethyl)ceph-3-em-4-carboxylate

Product 1

HCID 88512320(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-[(Z)-(3-methoxy-4-methyl-5-oxofuran-2-ylidene)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 81%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-15 °C

Procedure

Sodium 2-(2-tritylaminothiazol-4-yl)-2-Z-trityloxyiminoacetate (0.759 g), in dry DMF (5 mls) was cooled to ca -50° C. under argon. This solution was treated with methanesulphonyl chloride (0.085 mls) and allowed to warm to -15° C. A solution of diphenylmethyl 7β-amino-3-(Z-2,5-dihydro-4-methoxy-3-methyl-2-oxofuran-5-ylidenemethyl)ceph-3-em-4-carboxylate, (0.46 g) in dry DMF (5 mls) was added, and the solution allowed to reach room temperature over 1 h. The solution was diluted with ethl acetate and washed with water, brine and then dried. After removal of solvent the residue was flash chromatographed on silica gel eluting with 50% ethyl acetate/hexane to give the title compound as a yellow foam, (0.375 g, 36%), νmax 3380, 1770(br), 1725, 1685, 1630, 1505(br), 1440, 1370 and 1345cm-1 ; δH (CDCl3) 2.07 (3H,s), 3.74 and 3.96 (2H,ABq, J18.3Hz, sharpens on D2O shake), 5.08 (1H, m, sharpens to d, J5.0Hz on D2O shake), 6.12 (1H, br.m, sharpens to d, J5.0Hz on D2O shake), 6.43 (1H, br.s, sharpens on D2O shake), 6.74 (1H, s), 6.78 (1H, br.s, exch.), 6.98 (1H, s) and 7.20 to 7.55 (40H, m, arom-H); [mass spectrum: +ve ion (NOBA, Na+) MNa+, 1180].

Workup

  1. washwashed with water, brine
  2. customdried
  3. customAfter removal of solvent the residue
  4. customchromatographed on silica gel eluting with 50% ethyl acetate/hexane

Sources & evidence

ORD record
ord-65c68cc9887248d0b737782433fbe60d
Source dataset
uspto-grants-1991_11
Patent number
US05064649

Reaction notes

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