1,1'-Carbonyldiimidazole → ethyl (5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylate

HRID 1826204Notes

Reaction equation

HRID 1826204 reaction equation
[F:1][C:2]1[CH:3]=C(C=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)N.[O:15]1C[C@@H:16]1[C:17]([O:19][CH2:20][CH3:21])=[O:18].[O-]S(C(F)(F)F)(=O)=O.[Li+].[C:32]([N:39]1[CH:43]=[CH:42]N=[CH:40]1)(N1C=CN=C1)=[O:33]>C(#N)C>[F:1][C:2]1[CH:3]=[C:43]([N:39]2[CH2:40][C@H:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[O:15][C:32]2=[O:33])[CH:42]=[CH:7][C:8]=1[N:9]1[CH2:10][CH2:11][O:12][CH2:13][CH2:14]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 14853303-Fluoro-4-morpholinoanilineHCID 1512667ethyl (2R)-oxirane-2-carboxylateHCID 3664839Trifluoromethanesulfonic acid, lithium salt

Product 1

HCID 86590830ethyl (5R)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinecarboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3-fluoro-4-morpholinoaniline (J. Med. Chem. 1996, 39(3), 673-679, 0.796 g, 4.0 mmol), ethyl 2(R)-epoxypropanoate (0.696 g, 6.0 mmol) and lithium triflate (0.97 g, 6.2 mmol) in acetonitrile (12 mL) was stirred at 50-60° C. overnight. Solvent and excess epoxide was removed under reduced pressure, and the crude amino alcohol was redissolved in dry acetonitrile (40 mL) and 1,1′-carbonyldiimidazole (1.46 g, 9.0 mmol) was added. The mixture was stirred at ambient temperature overnight, and then the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (70 mL) and 3% aqueous citric acid (100 mL), the layers are separated, and the organic phase was washed with 3% aqueous citric acid (3×100 mL), water and saline, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product mixture was then purified by silica gel chromatography, eluting with ethanol/methylene chloride (2/98), and the appropriate fractions are pooled and concentrated to give the title compound, MS (ESI+) for C16H19N2O5F m/z 339 (M+H)+.

Workup

  1. customSolvent and excess epoxide was removed under reduced pressure
  2. dissolutionthe crude amino alcohol was redissolved in dry acetonitrile (40 mL)
  3. customthe solvent was removed under reduced pressure
  4. customThe residue was partitioned between ethyl acetate (70 mL) and 3% aqueous citric acid (100 mL)
  5. customthe layers are separated
  6. washthe organic phase was washed with 3% aqueous citric acid (3×100 mL), water and saline
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe product mixture was then purified by silica gel chromatography
  10. washeluting with ethanol/methylene chloride (2/98)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-fdf6e3ea18aa40a2b533d2228ec844db
Source dataset
uspto-grants-2006_05
Patent number
US07049443B2

Reaction notes

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