Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → HCID 69939367, compound

HRID 1058302Notes

Reaction equation

HRID 1058302 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[CH2:11]([C@@H:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:46])[CH2:25][C@H:26]([C:33]1[CH:34]=[C:35]([CH:43]=[CH:44][CH:45]=1)[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1(S(N2C(C3C=CC=CC=3)O2)(=O)=[O:54])C=CC=CC=1.C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>C1COCC1>[CH2:11]([C@@H:18]1[CH2:22][O:21][C:20](=[O:23])[N:19]1[C:24](=[O:46])[C@H:25]([OH:54])[C@H:26]([C:33]1[CH:34]=[C:35]([CH:43]=[CH:44][CH:45]=1)[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 3204052-(Benzenesulfonyl)-3-phenyloxaziridineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 69939689HCID 69939689, compound

Product 1

HCID 69939367HCID 69939367, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

To a cooled solution (−78° C.) of sodium hexamethyldisilazide (0.38 mL, 0.38 mmol) in THF (0.5 mL) was added tert-butyl 3-{(1R)-3-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxo-1-pyridin-2-ylpropyl}benzoate from the previous step (0.153 g, 0.314 mmol) in THF (1 mL) dropwise and stirred for 45 min. 2-(Phenysulfonyl)-3-phenyloxaziridine (0.167 g, 0.629 mmol) dissolved in THF (0.5 mL) was added to cold solution and the mixture was stirred for 10 min. Camphorsulfonic acid, dissolved in THF (2 mL), was quickly added and the bath was removed. The reaction was warmed to room temperature, diluted with saturated aqueous NaHCO3, extracted with EtOAc, washed with saturated aqueous NaHCO3 and brine, dried over MgSO4, filtered, and the solvent removed under reduced pressure. The residue was chromatographed on a 35 g ISCO column using 0-50% EtOAc/hexanes over 40 min and the lowest spot fractions were combined and the solvent removed under reduced pressure to give an oil. This oil was purified by preparative HPLC on a Waters PrepPak using 10% to 100% CH3CN/H2O with 0.1% TFA as eluant over 60 min. The product-containing fractions were combined and the acetonitrile was removed under reduced pressure. The remaining aqueous solution was basicified with saturated aqueous NaHCO3, extracted with 4×20 mL CH2Cl2, dried over Na2SO4 and filtered. The filtrate solvent was removed under reduced pressure to give tert-butyl 3-{(1R,2R)-3-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-2-hydroxy-3-oxo-1-pyridin-2-ylpropyl}benzoate as an oil (0.068 g, 43%). TLC Rf=0.3 (1:1 EtOAc:hexanes, UV visualization); HPLC RT=2.61 min, method B; M+H=503.

Workup

  1. additionwas added to cold solution
  2. stirringthe mixture was stirred for 10 min
  3. additionwas quickly added
  4. customthe bath was removed
  5. additiondiluted with saturated aqueous NaHCO3
  6. extractionextracted with EtOAc
  7. washwashed with saturated aqueous NaHCO3 and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customthe solvent removed under reduced pressure
  11. customThe residue was chromatographed on a 35 g ISCO column
  12. customover 40 min
  13. customthe solvent removed under reduced pressure
  14. customto give an oil
  15. customThis oil was purified by preparative HPLC on a Waters PrepPak
  16. customover 60 min
  17. customthe acetonitrile was removed under reduced pressure
  18. extractionextracted with 4×20 mL CH2Cl2
  19. dry with materialdried over Na2SO4
  20. filtrationfiltered
  21. customThe filtrate solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-e86f4292cb154f959e88e8ff0834d4a4
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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