Hydrogen Peroxide → (S)-Benzyl-3-[3-(3-benzyloxyphenyl)-3-hydroxy-2(S)-isopropoxypropionyl]oxazolidin-2-one

HRID 1985385Notes

Reaction equation

HRID 1985385 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:20])[CH2:15][O:16][CH:17]([CH3:19])[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-]S(C(F)(F)F)(=O)=O.C([B+]CCCC)CCC.[CH2:38]([O:45][C:46]1[CH:47]=[C:48]([CH:51]=[CH:52][CH:53]=1)[CH:49]=[O:50])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.P([O-])([O-])(O)=O.[Na+].[Na+].OO>C1(C)C=CC=CC=1.ClCCl.CO.C(N(CC)CC)C>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:20])[C@@H:15]([O:16][CH:17]([CH3:18])[CH3:19])[CH:49]([C:48]1[CH:51]=[CH:52][CH:53]=[C:46]([O:45][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:47]=1)[OH:50])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 5

HCID 784Hydrogen PeroxideHCID 743423-Benzyloxybenzaldehyde2×HCID 22026567Citric acid disodium phosphateHCID 59997951(4S)-4-benzyl-3-(2-isopropoxyacetyl)oxazolidin-2-oneHCID 178418657HCID 178418657, compound

Product 1

HCID 69008493(S)-Benzyl-3-[3-(3-benzyloxyphenyl)-3-hydroxy-2(S)-isopropoxypropionyl]oxazolidin-2-oneYield 109.2%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-75 °C

Procedure

After cooling a solution containing 8.1 g of (4S)-4-benzyl-3-(2-isopropoxyacetyl)-1,3-oxazolidin-2-one in toluene (120 ml) was cooled to −75° C., 5.0 ml of triethylamine was added. 30.5 ml of dibutylboron triflate (1M solution in dichloromethane) was added dropwise at such a rate that the inside temperature did not exceed −70° C. After the dropwise addition, the mixture was stirred for 50 minutes. Then, the inside temperature was raised to 0° C. and the mixture was stirred for another 50 minutes, and again cooled to −75° C. To the reaction solution was added a solution containing 5.2 g of 3-benzyloxybenzaldehyde in dichloromethane (25 ml) by means of cannula, and stirring was continued at −75° C. for 30 minutes. Then, the inside temperature was raised to 0° C. over about 1 hour by 10° C. per 10 minutes. Again after cooling to −75° C., a solution containing 2.0 g of 3-benzyloxybenzaldehyde in dichloromethane (10 ml) was added. The temperature was gradually raised to room temperature and stirred for 3 days at room temperature. The reaction solution was poured into a mixed solution of 150 ml of methanol, 100 ml of pH 7 buffer (disodium hydrogen phosphate-citric acid) and 30 ml of hydrogen peroxide (30% aqueous solution), and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was purified by silica gel column chromatography, to give 13.1 g of 4 (S)-benzyl-3-[3-(3-benzyloxyphenyl)-3-hydroxy-2 (S)-isopropoxypropionyl]oxazolidin-2-one as a colorless oil in the 2:1→3:2 hexane-ethyl acetate fraction.

Workup

  1. temperatureAfter cooling a solution
  2. customdid not exceed −70° C
  3. additionAfter the dropwise addition
  4. temperatureThen, the inside temperature was raised to 0° C.
  5. stirringthe mixture was stirred for another 50 minutes
  6. temperatureagain cooled to −75° C
  7. additionTo the reaction solution was added a solution
  8. stirringstirring
  9. waitwas continued at −75° C. for 30 minutes
  10. temperatureThen, the inside temperature was raised to 0° C. over about 1 hour by 10° C. per 10 minutes
  11. temperatureAgain after cooling to −75° C.
  12. additionwas added
  13. temperatureThe temperature was gradually raised to room temperature
  14. stirringstirred for 3 days at room temperature
  15. extractionextracted with ethyl acetate
  16. washThe organic layer was washed with saturated brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customthe solvent was evaporated
  19. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-d9ba1358e0fc42848f98debec567f3c3
Source dataset
uspto-grants-2009_06
Patent number
US07544835B2

Reaction notes

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