Sodium Bicarbonate → (6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(E)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 247762Notes

Reaction equation

HRID 247762 reaction equation
Cl.[NH2:2][CH:3]1[C:29](=[O:30])[N:5]2[C:6]([C:13]([O:15]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:14])=[C:7](/[CH:10]=[CH:11]\[CH3:12])[CH2:8][S:9][C@H:4]12.C(=O)(O)[O-].[Na+].[NH2:36][C:37]1[S:38][CH:39]=[C:40](/[C:42](=[N:55]/[O:56][CH3:57])/[C:43](ON2C3C=CC=CC=3N=N2)=[O:44])[N:41]=1>CN(C=O)C>[NH2:36][C:37]1[S:38][CH:39]=[C:40](/[C:42](=[N:55]/[O:56][CH3:57])/[C:43]([NH:2][CH:3]2[C:29](=[O:30])[N:5]3[C:6]([C:13]([OH:15])=[O:14])=[C:7](/[CH:10]=[CH:11]/[CH3:12])[CH2:8][S:9][C@H:4]23)=[O:44])[N:41]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 102453094-{(1Z)-2-[(1H-Benzotriazol-1-yl)oxy]-N-methoxy-2-oxoethanimidoyl}-1,3-thiazol-2-amineHCID 69989684diphenylmethyl 7-amino-3-[(Z)-1-propenyl]-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 88669955(6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(E)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 117%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 7-amino-3-trans-propenyl derivatives XIII (E, R3 =R4a =H) (720 mg, 3 m moles) and sodium bicarbonate (504 mg, 6 m moles) in 50% DMF (60 ml) was added 1-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetoxy]benzotriazole (954 mg, 3 m moles) and the mixture was stirred for 30 min. An additional amount of the active ester (1.81 g, 6 m moles) was added in four portions at 30-min intervals. The mixture was stirred for additional 2 hr at room temperature and passed through a column packed with the packing of prepPAK-C18 cartridge (300 ml, Waters). The column was washed with water and then eluted successively with 10% methanol and 20% methanol. Fractions of 20% methanol eluate showing a peak at retention time 5.57 min by HPLC* were collected and evaporated to dryness. The residue was dissolved in methanol and filtered. The filtrate was concentrated to 5 ml and the residue was triturated with a mixture of ether-isopropyl ether to give 805 mg (63%) of the title compound, melting at 180° C. (grad. dec.), 80% pure by HPLC*.

Workup

  1. stirringThe mixture was stirred for additional 2 hr at room temperature
  2. washThe column was washed with water
  3. washeluted successively with 10% methanol and 20% methanol
  4. customwere collected
  5. customevaporated to dryness
  6. dissolutionThe residue was dissolved in methanol
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated to 5 ml
  9. customthe residue was triturated with a mixture of ether-isopropyl ether

Sources & evidence

ORD record
ord-11d2d1abda2e4d1e87113cb031700cde
Source dataset
uspto-grants-1987_11
Patent number
US04708955

Reaction notes

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