Pyridine → HCID 15428058, compound

HRID 617754Notes

Reaction equation

HRID 617754 reaction equation
[C@H:1]12[CH2:26][C@H:4]([N:5]([C:7]3[CH:12]=[CH:11][C:10]([N:13]4[CH2:17][C@@H:16]([CH2:18]CS([O-])(=O)=O)[O:15][C:14]4=[O:24])=[CH:9][C:8]=3[F:25])[CH2:6]1)[CH2:3][S:2]2.[NH4+].[OH-].NCC1O[C:34](=[O:36])[NH:33]C1.N1C=CC=C[CH:38]=1.C(OC(=O)C)(=O)C.O1CCNC1=O>C(Cl)Cl.CO.C(Cl)(Cl)Cl.C1COCC1.CC(O)C>[F:25][C:8]1[CH:9]=[C:10]([N:13]2[CH2:17][C@H:16]([CH2:18][NH:33][C:34](=[O:36])[CH3:38])[O:15][C:14]2=[O:24])[CH:11]=[CH:12][C:7]=1[N:5]1[CH2:6][C@@H:1]2[CH2:26][C@H:4]1[CH2:3][S:2]2

Participants

10

Reactant 6

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 14923Ammonium HydroxideHCID 739492-OxazolidinoneHCID 105346455-(Aminomethyl)-1,3-oxazolidin-2-oneHCID 18391871HCID 18391871, compound

Product 1

HCID 15428058HCID 15428058, compound

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 21584188Chloroform methanolSolvent2×HCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of (R)[[3-[4[(1S,4S)-2-thia-5-azabicyclo[2.2.1]heptane-5-yl]-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]methanesulfonate (1.56 g, 3.88 mmol), 1:1 THF/i-PrOH (4 mL) and 30% NH4OH (4 mL) was heated to 95° C. in a sealed tube for 14 h and then cooled to ambient temperature. TLC analysis (5% MeOH/CHCl3) revealed the reaction to be complete. The mixture was diluted with CH2Cl2 (75 mL), washed with saturated aqueous NaHCO3 (15 mL) and brine (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a syrup. The crude 5-(aminomethyl)oxazolidinone intermediate was dissolved in CH2Cl2 (75 mL) and treated with pyridine (0.35 mL, 4.27 mmol) and acetic anhydride (0.403 mL, 4.27 mmol) at ambient temperature. After 1 h, TLC analysis (5% MeOH/CHCl3) indicated the elation to be completed. The reaction mixture was washed with H2O and brine, dried over Na2SO4, filtered and concentrated under reduced pressure to an amber solid. Chromatography over silica gel (125 g), eluting with 1-3% MeOH/CHCl3, afforded, after concentration of appropriate fractions, 1.23 g (87%) of the title oxazolidinone antibacterial agent as a solid with mp 90-95° C. and MS(EI) 365 (M+).

Workup

  1. temperaturecooled to ambient temperature
  2. customthe reaction
  3. washwashed with saturated aqueous NaHCO3 (15 mL) and brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a syrup
  8. washThe reaction mixture was washed with H2O and brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to an amber solid
  12. washChromatography over silica gel (125 g), eluting with 1-3% MeOH/CHCl3
  13. customafforded

Sources & evidence

ORD record
ord-6d4f93c9db5f45ed8ae62ff1b9973786
Source dataset
uspto-grants-1999_09
Patent number
US05952324

Reaction notes

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