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

HRID 723835

Reaction equation

HRID 723835 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) is stirred at 50–60° C. overnight. Solvent and excess epoxide is removed under reduced pressure, and the crude amino alcohol is redissolved in dry acetonitrile (40 mL) and 1,1′-carbonyldiimidazole (1.46 g, 9.0 mmol) is added. The mixture is stirred at ambient temperature overnight, and then the solvent is removed under reduced pressure. The residue is partitioned between ethyl acetate (70 mL) and 3% aqueous citric acid (100 mL), the layers are separated, and the organic phase is 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 is 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 is removed under reduced pressure
  2. dissolutionthe crude amino alcohol is redissolved in dry acetonitrile (40 mL)
  3. customthe solvent is removed under reduced pressure
  4. customThe residue is partitioned between ethyl acetate (70 mL) and 3% aqueous citric acid (100 mL)
  5. customthe layers are separated
  6. washthe organic phase is 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 is then purified by silica gel chromatography
  10. washeluting with ethanol/methylene chloride (2/98)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-e9872b4dd1d640c5b7f723e17a7eef47
Source dataset
uspto-grants-2006_11
Patent number
US07141588B2

Linked notes

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