Acetone → Penicillanic Acid

HRID 1679684Notes

Reaction equation

HRID 1679684 reaction equation
O=C1N2CCCCC2=NC=C1C([O-])=O.[Na+].CC(C)=O.ClC(OCC)=O.[CH3:26][C:27]1([CH3:49])[S:31][C@@H:30]2[C@H:32](NC([C@H](N)C3C=CC=CC=3)=O)[C:33](=[O:34])[N:29]2[C@H:28]1[C:46]([OH:48])=[O:47].O.O.O>CN1CCOCC1.[OH-].[Na+].CC(N(C)C)=O>[CH3:26][C:27]1([CH3:49])[S:31][C@@H:30]2[CH2:32][C:33](=[O:34])[N:29]2[C@H:28]1[C:46]([OH:48])=[O:47]

Participants

8

Reactant 4

HCID 180AcetoneHCID 10928Ethyl chloroformateHCID 23565Ampicillin TrihydrateHCID 23668906HCID 23668906, compound

Product 1

HCID 6891Penicillanic AcidYield 234.7%

Reagents, catalysts & solvents 3

HCID 79724-MethylmorpholineCatalystHCID 14798Sodium HydroxideSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-10 °C

Procedure

Sodium 6,7,8,9-tetrahydro-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylate (2mM, 0.432g.) was suspended in a mixture of dry acetone (25ml) and dry dimethylacetamide (2ml) and chilled to -10° C with stirring. Ethyl chloroformate (2mM, 0.2ml) and one drop of N-methyl morpholine were added and the reaction mixture stirred 20 minutes at -10° C. A solution of ampicillin trihydrate (2mM, 0.726g) in aqueous sodium hydroxide (0.489N, 3.64ml) was chilled and added to the mixed anhydride at -10° C. The reaction was stirred 1.75 hours to ambient temperature, the acetone evaporated, and the resulting solution diluted to 100ml with water, covered with ethyl acetate (50ml) and adjusted to pH 2.0 with 5N HCl. The organic layer was separated, the aqueous phase extracted with ethyl acetate (1 × 50ml), the organic extracts combined, washed with water (3 × 30ml), dried over magnesium sulphate to give the penicillanic acid as a white solid 0.85g. (85%), showing a single component on t.l.c., Rf 0.51 (chloroform/acetone/acetic acid; 7:7:1) δ [(CD3)2SO] 1.4, 1.55 (6H, 2 × s, gem dimethyls), 1.7 ##STR54## 4.17 (1H, s, C3 proton), 5.3 - 5.6 (2H, m, β-lactam protons), 5.87 (1H, d, α-proton), 7.1 - 7.5 (5H, m, aromatics), 8.5 (1H, s, pyrimidine proton), 9.2 - 10.0 (2H, 2 × d, 2 × NH); λmax (0.3% NaHCO3 solution) 206 (ε = 25,800), 230 (ε = 12,140) and 300 n.m. (ε = 11,000).

Workup

  1. stirringthe reaction mixture stirred 20 minutes at -10° C
  2. stirringThe reaction was stirred 1.75 hours to ambient temperature
  3. customthe acetone evaporated
  4. additionthe resulting solution diluted to 100ml with water
  5. customThe organic layer was separated
  6. extractionthe aqueous phase extracted with ethyl acetate (1 × 50ml)
  7. washwashed with water (3 × 30ml)
  8. dry with materialdried over magnesium sulphate

Sources & evidence

ORD record
ord-886eca48bb434e8a8e90b7ba6ebbba18
Source dataset
uspto-grants-1978_03
Patent number
US04081545

Reaction notes

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