Urea → Dicloxacillin sodium salt monohydrate

HRID 1680173Notes

Reaction equation

HRID 1680173 reaction equation
C(N(CC)CC)C.N[C:9](N)=[O:10].[CH3:12][C:13]1([CH3:25])[S:17][C@@H:16]2[C@H:18]([NH2:21])[C:19](=[O:20])[N:15]2[C@H:14]1[C:22]([OH:24])=[O:23].C[Si](C)(C)Cl.[Cl:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:33]=1[C:39]1[C:43](Cl)=[C:42]([CH3:45])[O:41][N:40]=1.[Na].C(C(CCCC)C([O-])=[O:51])C.[Na+:57]>C(Cl)Cl.CC(C)=O.O>[CH3:45][C:42]1[O:41][N:40]=[C:39]([C:33]2[C:32]([Cl:31])=[CH:37][CH:36]=[CH:35][C:34]=2[Cl:38])[C:43]=1[C:9]([NH:21][C@@H:18]1[C:19](=[O:20])[N:15]2[C@@H:14]([C:22]([O-:24])=[O:23])[C:13]([CH3:25])([CH3:12])[S:17][C@H:16]12)=[O:10].[OH2:51].[Na+:57]

Participants

11

Reactant 7

HCID 1176UreaHCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 110826-Aminopenicillanic acidHCID 5360545SodiumHCID 19861248HCID 19861248, compoundHCID 23672331Sodium 2-ethylhexanoate

Product 1

HCID 23675786Dicloxacillin sodium salt monohydrateYield 92%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

52.6% g (0.520 moles; purity 100%) of triethylamine were added to a stirred suspension of 18.0 g (0.300 moles; purity 100%) of urea and 43.2 g (0.198 moles; purity 99.0%) of 6-aminopenicillanic acid in 390 ml of methylene chloride at 20° C. Then 60.5 g (0.540 moles; purity 97.1%) of trimethylchlorosilane were added over 15 minutes, maintaining the temperature at 20° C. After 30 minutes of stirring, the temperature was raised to 40° C., and held for 60 minutes. The white suspension was cooled to -30° C., and 59.1 g (0.198 moles; purity 97.4%) of 3-(2',6'-dichlorophenyl)-5-methyl-4-isoxazolyl chloride were added; the temperature was allowed to increase to 0° C. and held at this value for a total time of 130 minutes. The suspension was added to a mixture of 180 ml of water and 390 ml of acetone, pre-cooled at 0° C. The aqueous layer was separated and discarded, and the organic layer was washed with 180 ml of water. The aqueous layer was separated and discarded, and the organic layer was dried over 50 g of anhydrous sodium sulphate. The product was precipitated as sodium salt monohydrate by addition of 0.200 moles of sodium 2-ethyl-hexanoate as a 1 N solution in acetone. The product was filtered off, washed with 450 ml of acetone and dried in an oven at 40° C. to yield 93.0 g of sodium dicloxacillin monohydrate (91.2% of the theoretical amount), as a white, crystalline powder. Water content 3.7%; spectrophotometric assay 98.3% on the anhydrous basis; specific rotation +133° on the anhydrous basis.

Workup

  1. temperaturethe temperature was raised to 40° C.
  2. waitheld for 60 minutes
  3. temperatureThe white suspension was cooled to -30° C.
  4. temperatureto increase to 0° C.
  5. customheld at this value for a total time of 130 minutes
  6. temperaturepre-cooled at 0° C
  7. customThe aqueous layer was separated
  8. washthe organic layer was washed with 180 ml of water
  9. customThe aqueous layer was separated
  10. dry with materialthe organic layer was dried over 50 g of anhydrous sodium sulphate
  11. filtrationThe product was filtered off
  12. washwashed with 450 ml of acetone
  13. customdried in an oven at 40° C.

Sources & evidence

ORD record
ord-505999a8ec574a1c85abed49c1c4e385
Source dataset
uspto-grants-1981_06
Patent number
US04272438

Reaction notes

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