Isopropanol → Potassium Clavulanate

HRID 127154

Reaction equation

HRID 127154 reaction equation
[Li+].[CH2:2]1[C:5](=[O:6])[N:4]2[C@@H:7]([C:13]([O-:15])=[O:14])/[C:8](/[O:12][C@H:3]12)=[CH:9]/[CH2:10][OH:11].C(O)(C)C.P([O-])([O-])([O-])=O.[K+:25].[K+].[K+].P([O-])([O-])([O-])=O.[Li+].[Li+].[Li+]>O>[CH2:2]1[C:5](=[O:6])[N:4]2[C@@H:7]([C:13]([O-:15])=[O:14])/[C:8](/[O:12][C@H:3]12)=[CH:9]/[CH2:10][OH:11].[K+:25]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 62657Potassium Phosphate, TribasicHCID 165867Lithium phosphateHCID 237146474-Oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, 3-(2-hydroxyethylidene)-7-oxo-, lithium salt (1:1), (2R,3Z,5R)-

Product 1

HCID 23665591Potassium Clavulanate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Lithium clavulanate (21.9 g, estimated purity 67% as pure free acid, 3/40 mole) was stirred in distilled water (135 mls) and isopropanol added (108 mls) with stirring and cooling in an ice bath. The supernatant liquid was decanted off the gummy precipitate (6.0 gm) and a solution (37.8 mls 1.5 eq) of 1 M potassium orthophosphate added slowly with about 20 mg lithium phosphate for seeding. As lithium phosphate separated the pH changed from 8.2 to 7.1 ending up at 7.65 on total addition. The mixture was made up to 500 mls with acetone and filtered and the clear yellow filtrate was divided into 3 equal portions. Portion 1 was made up to 600 mls with acetone, filtered via celite (2 gm) and added to 2.4 liters acetone slowly with stirring. The white solid was filtered off, washed with acetone and fluid bed dried to give potassium clavulanate (4.94 g, 82.1% pfa, 83% recovery). Portion 2 was made up to 800 mls, filtered as above and added to 2.2 l acetone. The solid was filtered off and dried to give potassium clavulanate (4.88 g, 81.9% pfa, 82% recovery). Portion 3 was made up to 1000 mls, filtered as above and added to 2 l acetone. The solid was filtered off and dried to give potassium clavulanate (4.84 g, 82.3 pfa, 82% recovery).

Workup

  1. temperaturecooling in an ice bath
  2. customThe supernatant liquid was decanted off the gummy precipitate (6.0 gm)
  3. customAs lithium phosphate separated the pH
  4. additionchanged from 8.2 to 7.1 ending up at 7.65 on total addition
  5. filtrationfiltered
  6. filtrationfiltered via celite (2 gm)
  7. additionadded to 2.4 liters acetone slowly
  8. stirringwith stirring
  9. filtrationThe white solid was filtered off
  10. washwashed with acetone and fluid bed
  11. customdried

Sources & evidence

ORD record
ord-535806152dcb4222b990ec60d35e69f0
Source dataset
uspto-grants-1981_03
Patent number
US04255332

Linked notes

Loading…