Reaction #2267052

ord-c3aa9180f2134a2c87d4796fe89c9112

Reaction equation

O=P([O-])(O)O.O=P([O-])([O-])O.[Cl-].[Cl-].[K+].[K+].[Na+].[Na+].[Na+]
phosphate-buffered saline
CC[C@H]1OC(=O)C[C@@H](O)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]2O)[C@@H](CCN2C[C@H](C)C[C@H](C)C2)C[C@@H](C)C(=O)/C=C/C(C)=C/[C@@H]1CO[C@@H]1O[C@H](C)[C@@H](O)[C@@H](OC)[C@H]1OC
tilmicosin
→
CC[C@H]1OC(=O)C[C@@H](O)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]2O)[C@@H](CCN2C[C@H](C)C[C@H](C)C2)C[C@@H](C)C(=O)/C=C/C(C)=C/[C@@H]1CO[C@@H]1O[C@H](C)[C@@H](O)[C@@H](OC)[C@H]1OC
tilmicosin
CCCCCCCCCCCC(=O)O
lauric acid
CCCCCCCCCC(=O)O
decanoic acid

Reactants

—
carboxylic acids
O=P([O-])(O)O.O=P([O-])([O-])O.[Cl-].[Cl-].[K+].[K+].[Na+].[Na+].[Na+]
phosphate-buffered saline
CC[C@H]1OC(=O)C[C@@H](O)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)[C@@H](O)[C@H](N(C)C)[C@H]2O)[C@@H](CCN2C[C@H](C)C[C@H](C)C2)C[C@@H](C)C(=O)/C=C/C(C)=C/[C@@H]1CO[C@@H]1O[C@H](C)[C@@H](O)[C@@H](OC)[C@H]1OC
tilmicosin

Reagents

None

Solvents

CN1CCCC1=O
N-methyl-pyrrolidone

Conditions

Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    Otherto obtain a clear solution
  2. 2
    OtherOne ml aliquots of these solutions were sealed in dialysis bags
  3. 3
    Otherthe bags were suspended in flasks
  4. 4
    Otherto precipitate in the bag within about 1 hour
  5. 5
    OtherAliquots of saline were removed at various intervals and tilmicosin

Procedure

10 grams (0.0115 moles) of tilmicosin and 0.0253 moles of various carboxylic acids (such as, for example, decanoic, lauric, linoleic, or myristic acids, in individual assays) were taken in a flask and made up to a final volume of 100 ml with N-methyl-pyrrolidone and stirred for 60 minutes to obtain a clear solution. One ml aliquots of these solutions were sealed in dialysis bags, and the bags were suspended in flasks containing 150 ml of phosphate-buffered saline, pH 7.4. The salt was observed to precipitate in the bag within about 1 hour. Aliquots of saline were removed at various intervals and tilmicosin was determined by HPLC. The results with decanoic acid (C-10) and lauric acid (C-12) salts in FIG. 3 show that tilmicosin continued to diffuse out of the bag for more than 120 hours. Longer chain length acids caused a slower release of tilmicosin. Micotil® (Eli Lilly, Indianapolis, Ind.), a phosphate salt of tilmicosin, is readily soluble and rapidly diffuses from the bag.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US06887487B2uspto-grants-2005_05