Hydrochloric Acid → (6R,7R)-7-[[(2Z)-2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-methoxyiminoacetyl]amino]-8-oxo-3-(3-oxobutanoyloxymethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 1761426Notes

Reaction equation

HRID 1761426 reaction equation
[NH2:1][C@@H:2]1[C:20](=[O:21])[N:4]2[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9][O:10][C:11](=[O:16])[CH2:12][C:13](=[O:15])[CH3:14])[CH2:7][S:8][C@H:3]12.C(=O)([O-])O.[Na+].Cl.[Cl:28][CH2:29][C:30]([NH:32][C:33]1[S:34][CH:35]=[C:36](/[C:38](=[N:42]/[O:43][CH3:44])/[C:39](Cl)=[O:40])[N:37]=1)=[O:31].Cl>O.O1CCCC1>[Cl:28][CH2:29][C:30]([NH:32][C:33]1[S:34][CH:35]=[C:36](/[C:38](=[N:42]/[O:43][CH3:44])/[C:39]([NH:1][C@@H:2]2[C:20](=[O:21])[N:4]3[C:5]([C:17]([OH:19])=[O:18])=[C:6]([CH2:9][O:10][C:11](=[O:16])[CH2:12][C:13](=[O:15])[CH3:14])[CH2:7][S:8][C@H:3]23)=[O:40])[N:37]=1)=[O:31]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 117819897beta-Amino-3(3-oxobutyryloxymethyl)-3-cephem-4-carboxylic acidHCID 12884125(2Z)-2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-methoxyiminoacetyl chloride;hydrochloride

Product 1

HCID 13457838(6R,7R)-7-[[(2Z)-2-[2-[(2-chloroacetyl)amino]-1,3-thiazol-4-yl]-2-methoxyiminoacetyl]amino]-8-oxo-3-(3-oxobutanoyloxymethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

7β-Amino-3-(3-oxobutyryloxymethyl)-3-cephem-4-carboxylic acid, 157 g, is suspended in a mixture consisting of 500 ml of tetrahydrofuran and 500 ml of water, and to this, 141 g of sodium hydrogen carbonate is added in small portions with stirring. With stirring at 5° C., 150 g of 2-(2-chloroacetamidothiazol-4-yl)-2(Z)-methoxyiminoacetylchloride hydrochloride is added over 20 minutes, and the reaction mixture is stirred for further 1 hour at the same temperature. After completion of the reaction, the pH is adjusted to 3.0 with 10% hydrochloric acid, and the reaction mixture is extracted twice with 1 liter each of a mixture of ethyl acetate-tetrahydrofuran (1:1). The extract is dried over anhydrous magnesium sulfate, the solvent is evaporated off under reduced pressure to leave colorless powder, which is washed with 200 ml of ethyl acetate and filtered, to give 253 g of the desired compound.

Workup

  1. stirringWith stirring at 5° C.
  2. stirringthe reaction mixture is stirred for further 1 hour at the same temperature
  3. customAfter completion of the reaction
  4. extractionthe reaction mixture is extracted twice with 1 liter each of a mixture of ethyl acetate-tetrahydrofuran (1:1)
  5. dry with materialThe extract is dried over anhydrous magnesium sulfate
  6. customthe solvent is evaporated off under reduced pressure
  7. customto leave colorless powder, which
  8. washis washed with 200 ml of ethyl acetate
  9. filtrationfiltered

Sources & evidence

ORD record
ord-ba1f40f27c5747f7928205ef2e088458
Source dataset
uspto-grants-1989_05
Patent number
US04826834

Reaction notes

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