p-Toluenesulfonic acid → HCID 15550202, compound

HRID 379318Notes

Reaction equation

HRID 379318 reaction equation
[C:1]1([C:7]2[N:8]=[C:9]([C@:18]3(O)[C@@H:23]([OH:24])[CH2:22][CH2:21][CH2:20][C@H:19]3[CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([O:32][Si](C(C)(C)C)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:27]=3)[O:10][C:11]=2C2C=CC=CC=2)[CH:6]=[CH:5]C=C[CH:2]=1.[CH3:51][O:52][C:53]([O:57]C)(OC)[CH3:54].[C:59]1(C)[CH:64]=[CH:63][C:62](S(O)(=O)=O)=[CH:61][CH:60]=1.[F-].[CH2:71]([N+](CCCC)(CCCC)CCCC)[CH2:72]CC.[CH2:88](Cl)Cl>C1COCC1.CCOC(C)=O>[C:1]1([C:7]2[N:8]=[C:9]([C@:18]34[O:24][C@H:23]3[CH2:22][CH2:21][CH2:20][C@H:19]4[CH2:25][C:26]3[CH:27]=[C:28]([CH:29]=[CH:30][CH:31]=3)[O:32][CH2:54][C:53]([O:52][CH2:51][CH3:88])=[O:57])[O:10][C:11]=2[C:59]2[CH:60]=[CH:61][CH:62]=[CH:63][CH:64]=2)[CH:6]=[CH:5][CH:72]=[CH:71][CH:2]=1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 6344DichloromethaneHCID 15050Trimethyl orthoacetateHCID 2724141Tetrabutylammonium FluorideHCID 15550205HCID 15550205, compound

Product 1

HCID 15550202HCID 15550202, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1S,2R,3S)-2-(4,5-diphenyloxazol-2-yl)-2,3-dihydroxy-1-[3-(tertbutyldiphenylsiloxy)benzyl] cyclohexane (8.7 g) in CH2Cl2 (100 ml) were added orthoacetic acid trimethyl ester (2.8 ml) and p-toluenesulfonic acid (150 mg) at room temperature under N2 gas. After being stirred for 30 minutes, the mixture was evaporated in vacuo. The residue was diluted with CH2Cl2 (100 ml), followed by addition of acetylbromide (3.0 ml) at 0° C. under N2 gas. After being stirred for 2 hours at room temperature, the mixture was evaporated in vacuo. The residue was diluted with MeOH (100 ml) and added with K2CO3 (5 g) at room temperature. The mixture was stirred for 2 hours at the same temperature and then partitioned between EtOAc and water. The organic layer was washed with 1N-HCl solution, water, sat. NaHCO3 solution and brine. The organic solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel to give an oily compound. The oily compound was dissolved in THF (50 ml), followed by addition of tetrabutylammonium fluoride (15 ml, 1M solution in THF) at room temperature. After being stirred for 4 hours, the mixture was diluted with EtOAc. The mixture was washed with 1N-HCl solution and brine and evaporated. The residue was dissolved in DMF (50 ml), followed by addition of K2CO3 (5 g) and ethyl bromoacetate (2.0 ml) at room temperature. The mixture was stirred for 2 hours at the same temperature and partitioned between EtOAc and water. The organic layer was washed with water and brine and evaporated in vacuo. The residue was purified by chromatography on silica gel to give ethyl {3-{[(1S,2R,3S)-2-(4,5-diphenyloxazol-2-yl)-2,3-epoxy-1-cyclohexyl]methyl}phenoxy}acetate (4.3 g).

Workup

  1. customthe mixture was evaporated in vacuo
  2. additionThe residue was diluted with CH2Cl2 (100 ml)
  3. additionfollowed by addition of acetylbromide (3.0 ml) at 0° C. under N2 gas
  4. stirringAfter being stirred for 2 hours at room temperature
  5. customthe mixture was evaporated in vacuo
  6. additionThe residue was diluted with MeOH (100 ml)
  7. additionadded with K2CO3 (5 g) at room temperature
  8. stirringThe mixture was stirred for 2 hours at the same temperature
  9. custompartitioned between EtOAc and water
  10. washThe organic layer was washed with 1N-HCl solution, water, sat. NaHCO3 solution and brine
  11. customThe organic solvent was evaporated in vacuo
  12. customThe residue was purified by chromatography on silica gel
  13. customto give an oily compound
  14. stirringAfter being stirred for 4 hours
  15. washThe mixture was washed with 1N-HCl solution and brine
  16. customevaporated
  17. dissolutionThe residue was dissolved in DMF (50 ml)
  18. additionfollowed by addition of K2CO3 (5 g) and ethyl bromoacetate (2.0 ml) at room temperature
  19. stirringThe mixture was stirred for 2 hours at the same temperature
  20. custompartitioned between EtOAc and water
  21. washThe organic layer was washed with water and brine
  22. customevaporated in vacuo
  23. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-adf949d2bb164e91a6912b8c9adab2b2
Source dataset
uspto-grants-2001_10
Patent number
US06297267B1

Reaction notes

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