Dimethyl Sulfoxide → (5S)-3-(4-(3,6-Dihydro-2H-pyran-4-yl)-3-fluorophenyl)-5-(3-methyl-2-oxo-2,3-dihydroimidazol-1-ylmethyl)oxazolidin-2-one

HRID 723779Notes

Reaction equation

HRID 723779 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][NH:4][C:3]1=[O:7].[H-].[Na+].[O:10]1[CH2:15][CH:14]=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:26][C@H:25](COS(C)(=O)=O)[O:24][C:23]3=[O:33])=[CH:18][C:17]=2[F:34])[CH2:12][CH2:11]1.[CH3:35]S(C)=O>>[O:10]1[CH2:11][CH:12]=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([N:22]3[CH2:26][C@H:25]([CH2:1][N:2]4[CH:6]=[CH:5][N:4]([CH3:35])[C:3]4=[O:7])[O:24][C:23]3=[O:33])=[CH:18][C:17]=2[F:34])[CH2:14][CH2:15]1

Participants

5

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 24758Sodium hydrideHCID 5676001-Methylimidazolidin-2-oneHCID 213566765(R)-methanesulfonyloxymethyl 3-(4-[3,6-dihydro-(2H)-pyran-4-yl]-3-fluorophenyl)oxazolidin-2-one

Product 1

HCID 69364850(5S)-3-(4-(3,6-Dihydro-2H-pyran-4-yl)-3-fluorophenyl)-5-(3-methyl-2-oxo-2,3-dihydroimidazol-1-ylmethyl)oxazolidin-2-one

Procedure

A solution of 1-methylimidazolidin-2-one (80 mg, 0.82 mM, Heterocycles, 1987, 26, 3153) in dimethylsulfoxide (1 ml) was treated with sodium hydride (55% in oil, 40 mg, 0.92 mM) at ambient temperature under nitrogen. After stirring for 20 minutes, (5R)-3-(4-(3,6-dihydro-2H-pyran-4-yl)-3-fluorophenyl)-5-methanesulfonyloxymethyloxazolidin-2-one (300 mg, 0.81 mM; WO 97-09328) in dimethylsulfoxide (1.5 ml) was added and stirring continued for 1.5 hours. The temperature was then progressively raised to 85°, and heated at this temperature for 24 hours. After cooling and dilution with water (50 ml), the mixture was extracted with ethyl acetate (3×30 ml), and combined extracts washed with brine (20 ml). After drying (magnesium sulfate) and evaporation, the residue was purified by chromatography on a 10 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 6% methanol in dichloromethane. Relevant fractions were combined to give the title product (60 mg).

Workup

  1. stirringstirring
  2. waitcontinued for 1.5 hours
  3. temperatureThe temperature was then progressively raised to 85°
  4. temperatureheated at this temperature for 24 hours
  5. temperatureAfter cooling
  6. extractiondilution with water (50 ml), the mixture was extracted with ethyl acetate (3×30 ml)
  7. washwashed with brine (20 ml)
  8. customAfter drying
  9. custom(magnesium sulfate) and evaporation
  10. customthe residue was purified by chromatography on a 10 g silica Mega Bond Elut® column
  11. washeluting with
  12. temperaturea gradient increasing in polarity from 0 to 6% methanol in dichloromethane

Sources & evidence

ORD record
ord-f86dd80c93ed4849bbc00ad771eb529d
Source dataset
uspto-grants-2006_11
Patent number
US07141583B2

Reaction notes

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