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

HRID 1421790Notes

Reaction equation

HRID 1421790 reaction equation
CS(Cl)(=O)=O.C([NH:25][C:26]1[S:27][CH:28]=[C:29](/[C:31](=[N:35]/[O:36]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)/[C:32]([O-:34])=O)[N:30]=1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Na+].[NH2:57][C@@H:58]1[C:77](=[O:78])[N:60]2[C:61]([C:70]([O:72]C(C)(C)C)=[O:71])=[C:62]([C@H:65]3[CH2:69][CH2:68][CH2:67][O:66]3)[CH2:63][S:64][C@H:59]12.N1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[NH2:25][C:26]1[S:27][CH:28]=[C:29](/[C:31](=[N:35]/[OH:36])/[C:32]([NH:57][C@@H:58]2[C:77](=[O:78])[N:60]3[C:61]([C:70]([OH:72])=[O:71])=[C:62]([CH:65]4[CH2:69][CH2:68][CH2:67][O:66]4)[CH2:63][S:64][C@H:59]23)=[O:34])[N:30]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 10381740t-butyl (6R,7R)-7-amino-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylateHCID 23714200sodium (2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetate

Product 1

HCID 88236883(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(oxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 151.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

Methanesulphonyl chloride (96 μl, 1.25 mmol) was added to sodium 2-(2-tritylaminothiazol-4-yl)-2-(Z)-trityloxyiminoacetate (852 mg, 1.2 mmol) in DMF (2 ml) at <-40° C. The mixture was stirred 0.5 h at -30±10° C. then t-butyl (6R,7R)-7-amino-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (326 mg, 1 mmol) in DMF (2 ml), followed by pyridine (101 μl, 1.25 mmol), were added. The reaction was stirred for 1 h without further cooling then diluted with ethyl acetate, washed twice with water and with brine, dried, concentrated in vacuo and flash chromatographed eluting with 25, 30% ethyl acetate in hexane to give the title compound as a colourless foam (665 mg, 68%); νmax (CH2Cl2) 3395, 1787, 1722, 1687, 1527, 1449, 1156 and 1051 cm-1 ; δH (CDCl3 /CD3OH) 1.55 (9H, s), 1.65-2.25 (4H, m), 3.32 and 3.40 (2H, ABq, J 17.6 Hz), 3.8-4.0 (2H, m), 5.08 (1H, d, J 4.8 Hz), 5.13 (1H, dd, J 7.0, 8.1 Hz), 5.91 (1H, d, J 4.5 Hz), 6.56 (1H, s), 7.2-7.5 (30H, m). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (1002)].

Workup

  1. additionwere added
  2. stirringThe reaction was stirred for 1 h
  3. temperaturewithout further cooling
  4. washwashed twice with water and with brine
  5. customdried
  6. concentrationconcentrated in vacuo and flash
  7. customchromatographed
  8. washeluting with 25, 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-3edf369e0f85437e846044a57c6911ff
Source dataset
uspto-grants-2000_06
Patent number
US06077952

Reaction notes

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