Phosphate → 2-(R)-[2-(S)-Benzyl-1-(S)-hydroxy-3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)-3-oxopropyl]-4-(R)-fluoropyrrolidine-1-carboxylic acid tert-butyl ester

HRID 732360Notes

Reaction equation

HRID 732360 reaction equation
[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC.[CH:18]([C@H:21]1[CH2:25][O:24][C:23](=[O:26])[N:22]1[C:27](=[O:36])[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([CH3:20])[CH3:19].C(N(CC)C(C)C)(C)C.[C:46]([O:50][C:51]([N:53]1[CH2:57][C@H:56]([F:58])[CH2:55][C@@H:54]1[CH:59]=[O:60])=[O:52])([CH3:49])([CH3:48])[CH3:47].P([O-])([O-])([O-])=O>ClCCl>[C:46]([O:50][C:51]([N:53]1[CH2:57][C@H:56]([F:58])[CH2:55][C@@H:54]1[C@@H:59]([OH:60])[C@H:28]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:27]([N:22]1[C@@H:21]([CH:18]([CH3:20])[CH3:19])[CH2:25][O:24][C:23]1=[O:26])=[O:36])=[O:52])([CH3:49])([CH3:48])[CH3:47]

Participants

7

Reactant 5

HCID 1061PhosphateHCID 81531DiisopropylethylamineHCID 10467835(S)-4-isopropyl-3-(3-phenylpropanoyl)oxazolidin-2-oneHCID 86614994HCID 86614994, compoundHCID 178418657HCID 178418657, compound

Product 1

HCID 688147272-(R)-[2-(S)-Benzyl-1-(S)-hydroxy-3-(4-(S)-isopropyl-2-oxo-oxazolidin-3-yl)-3-oxopropyl]-4-(R)-fluoropyrrolidine-1-carboxylic acid tert-butyl esterYield 52.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

Add dibutylboron triflate (1 M in dichloromethane, 11.8 mL, 11.8 mmol) to a solution of 4-(S)-isopropyl-3-(3-phenylpropionyl)-oxazolidin-2-one (2.8 g, 10.7 mmol) in dichloromethane (40 mL) at 0° C. Stir 5 min. Add N,N-diisopropylethylamine (2.25 mL, 12.87 mmol) and stir 90 min. Cool to −78° C. and add 4-(R)-fluoro-2-(R)-formylpyrrolidine-1-carboxylic acid tert-butyl ester (2.53 g, 11.6 mmol) in dichloromethane (15 mL) over 15 min. Stir 90 min and then warm to room temperature over 18 h. Cool in ice bath and add 0.05 M pH 7 phosphate buffer (15 mL). Extract with dichloromethane and concentrate. Dissolve in methanol (50 mL) and cool in ice bath. Add aqueous hydrogen peroxide (15 mL, 30% solution) and remove ice bath. Stir 5 min and concentrate. Extract with ethyl acetate and wash extract with 1 N HCl, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with hexanes and ethyl acetate) to give the title compound as a foam (2.68 g, 52%).

Workup

  1. stirringStir 90 min
  2. temperaturewarm to room temperature over 18 h
  3. temperatureCool in ice bath
  4. extractionExtract with dichloromethane
  5. concentrationconcentrate
  6. dissolutionDissolve in methanol (50 mL)
  7. temperaturecool in ice bath
  8. customAdd aqueous hydrogen peroxide (15 mL, 30% solution) and remove ice bath
  9. stirringStir 5 min
  10. concentrationconcentrate
  11. extractionExtract with ethyl acetate
  12. washwash
  13. extractionextract with 1 N HCl, saturated aqueous sodium bicarbonate, saturated aqueous sodium chloride
  14. dry with materialdry (magnesium sulfate)
  15. concentrationconcentrate
  16. custompurify
  17. wash(silica gel chromatography, eluting with hexanes and ethyl acetate)

Sources & evidence

ORD record
ord-b742167197d34da1b2af5f73233f34a7
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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