Methanol → 7-(2-Methoxyimino-3,3-diethoxy-4-chlorobutyramido)-3-hydroxycepham-4-carboxylic acid

HRID 1702082Notes

Reaction equation

HRID 1702082 reaction equation
CO.[NH2:3][CH:4]1[C:15](=[O:16])[N:6]2[CH:7]([C:12]([OH:14])=[O:13])[CH:8]([OH:11])[CH2:9][S:10][C@H:5]12.C(=O)(O)[O-].[Na+].[CH3:22][O:23][N:24]=[C:25]([C:29]([O:35][CH2:36][CH3:37])([O:32][CH2:33][CH3:34])[CH2:30][Cl:31])[C:26](Cl)=[O:27]>O.O1CCCC1>[CH3:22][O:23][N:24]=[C:25]([C:29]([O:35][CH2:36][CH3:37])([O:32][CH2:33][CH3:34])[CH2:30][Cl:31])[C:26]([NH:3][CH:4]1[C:15](=[O:16])[N:6]2[CH:7]([C:12]([OH:14])=[O:13])[CH:8]([OH:11])[CH2:9][S:10][C@H:5]12)=[O:27]

Participants

7

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 13072520(6R)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acidHCID 543636652-Methoxyimino-3,3-diethoxy-4-chlorobutyryl chloride

Product 1

HCID 867388377-(2-Methoxyimino-3,3-diethoxy-4-chlorobutyramido)-3-hydroxycepham-4-carboxylic acidYield 132.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methanol (40 ml) was added to a solution of 7-amino-3-hydroxycepham-4-carboxylic acid (2 g) and sodium bicarbonate (0.57 g) in water (13.4 g) under ice-cooling. A solution of 2-methoxyimino-3,3-diethoxy-4-chlorobutyryl chloride (syn isomer, 1.34 g) in dry tetrahydrofuran (2 ml) was added to a solution while adjusting pH 6.5 to 7.8, then and stirred under ice-cooling for three hours. After adjusting the resultant mixture to pH 7.5, the solvent was removed in vacuo. The aqueous residue was adjusted to pH 7.5 under ice-cooling, and diisopropyl ether (10 ml) was added to the solution. After the aqueous solution was separated, ethyl acetate (20 ml) was added to the aqueous solution, and adjusted to pH 2.0 with 20% sulfuric acid. The ethyl acetate layer was separated and the aqueous solution was extracted with ethyl acetate (10 ml) twice. The ethyl acetate layer and the extract were combined, washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solution was concentrated in vacuo to give 7-(2-methoxyimino-3,3-diethoxy-4-chlorobutyramido)-3-hydroxycepham-4-carboxylic acid (syn isomer, 2.97 g).

Workup

  1. temperaturecooling
  2. temperaturecooling for three hours
  3. customthe solvent was removed in vacuo
  4. temperaturecooling
  5. additiondiisopropyl ether (10 ml) was added to the solution
  6. customAfter the aqueous solution was separated
  7. additionethyl acetate (20 ml) was added to the aqueous solution
  8. customThe ethyl acetate layer was separated
  9. extractionthe aqueous solution was extracted with ethyl acetate (10 ml) twice
  10. washwashed with a saturated aqueous solution of sodium chloride
  11. dry with materialdried over magnesium sulfate
  12. concentrationThe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-0ad6534136a644f7b6c50d1b7dbc2fbf
Source dataset
uspto-grants-1983_04
Patent number
US04379922

Reaction notes

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