N,N'-Dimethylethylenediamine → (S)-3-(6-fluoropyridin-3-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one

HRID 525340Notes

Reaction equation

HRID 525340 reaction equation
[CH3:1][C:2]1([CH3:14])[O:6][C:5](=[O:7])[NH:4][C@H:3]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[F:15][C:16]1[CH:21]=[CH:20][C:19](I)=[CH:18][N:17]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CNCCNC>[Cu]I.O.O1CCOCC1>[F:15][C:16]1[N:17]=[CH:18][C:19]([N:4]2[C@@H:3]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:2]([CH3:14])([CH3:1])[O:6][C:5]2=[O:7])=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 2733820(S)-(+)-5,5-Dimethyl-4-phenyl-2-oxazolidinoneHCID 27831792-Fluoro-5-iodopyridine

Product 1

HCID 89813979(S)-3-(6-fluoropyridin-3-yl)-5,5-dimethyl-4-phenyloxazolidin-2-oneYield 72.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a round bottom flask were added (S)-5,5-dimethyl-4-phenyloxazolidin-2-one (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (0.750 g, 3.92 mmol), 2-fluoro-5-iodopyridine (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (1.749 g, 7.84 mmol), and dioxane (15.69 mL). Tribasic potassium phosphate (4.16 g, 19.61 mmol) was then added to the mixture. The vessel was purged with nitrogen followed by the addition of N,N′-dimethylethylenediamine (0.844 mL, 7.84 mmol) and copper (I) iodide (0.747 g, 3.92 mmol). The vessel was heated to reflux overnight providing an orange suspension. To the mixture was added water (˜10 mL), and the resulting slurry was filtered through Celite® brand filter aid. The yellow filtrate was transferred to a separatory funnel, diluted with water and extracted with EtOAc (2×). The combined organic layers were dried with Na2SO4, filtered, and dried under reduced pressure. The residue was purified with a 50 g SNAP column (Biotage) ramping EtOAc in heptane (0-35%, then isocratic at 35%) to elute (S)-3-(6-fluoropyridin-3-yl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.815 g, 2.85 mmol, 72.6% yield) which was obtained as a white solid upon drying. 1H NMR (400 MHz, CDCl3) δ=8.21 (ddd, J=3.0, 6.8, 9.0 Hz, 1H), 8.02-7.99 (m, 1H), 7.41-7.34 (m, 3H), 7.20-7.16 (m, 2H), 6.88 (ddd, J=0.6, 3.5, 8.9 Hz, 1H), 5.00 (s, 1H), 1.71 (s, 3H), 1.04 (s, 3H). m/z (ESI) 287.1 (M+H)+.

Workup

  1. customThe vessel was purged with nitrogen
  2. temperatureThe vessel was heated
  3. temperatureto reflux overnight
  4. customproviding an orange suspension
  5. filtrationthe resulting slurry was filtered through Celite® brand
  6. filtrationfilter aid
  7. customThe yellow filtrate was transferred to a separatory funnel
  8. additiondiluted with water
  9. extractionextracted with EtOAc (2×)
  10. dry with materialThe combined organic layers were dried with Na2SO4
  11. filtrationfiltered
  12. customdried under reduced pressure
  13. customThe residue was purified with a 50 g SNAP column (Biotage)

Sources & evidence

ORD record
ord-d6fe55e0ea2843459567eeba6faba1d5
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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