2,6-Lutidine → (3r,5r)-3-{[Tert-butyl(dimethyl)silyl]oxy}-5-{[tert-butyl(diphenyl)silyl]oxy}-4-methylenecyclohexanone

HRID 388738Notes

Reaction equation

HRID 388738 reaction equation
[Si:1]([O:18][C@@H:19]1[CH2:24][C@H:23]([O:25][Si](CC)(CC)CC)[CH2:22][C@@H:21]([OH:33])[C:20]1=[CH2:34])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(O[Si:49]([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50])(=O)=O>ClCCl>[Si:49]([O:33][C@H:21]1[C:20](=[CH2:34])[C@H:19]([O:18][Si:1]([C:14]([CH3:17])([CH3:16])[CH3:15])([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:24][C:23](=[O:25])[CH2:22]1)([C:52]([CH3:55])([CH3:54])[CH3:53])([CH3:51])[CH3:50]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 68936267(1r,3r,5r)-3-{[Tert-butyl(diphenyl)silyl]oxy}-2-methylene-5-[(triethylsilyl)oxy]cyclohexanol

Product 1

HCID 57696885(3r,5r)-3-{[Tert-butyl(dimethyl)silyl]oxy}-5-{[tert-butyl(diphenyl)silyl]oxy}-4-methylenecyclohexanoneYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The compound of Example 13D (8.5 g, 17 mmol) was dissolved in 50 mL of dichloromethane; 4.4 mL of 2,6-lutidine was added, and the resultant solution was cooled to 0° C. tert-Butyldimethylsilyl trifluoromethanesulfonate (5.9 mL) was added, and the mixture was stirred for 1 hour. The reaction was quenched by the addition of saturated aqueous NH4Cl, the solvents were removed in vacuo, and the residue was partitioned between ethyl acetate and water. The organic phase was washed with 1 N aqueous HCl, then brine, and dried over Na2SO4. The solvents were removed in vacuo; the residue was purified by chromatography on an Analogix IntelliFlash 280™, eluting with a gradient of 2% to 5% ethyl acetate in hexanes. The product (9.3 g) was dissolved in 75 mL of ethanol; pyridinium p-toluenesulfonate (390 mg) was added, and the mixture was stirred at ambient temperature for 1 hour. The solvents were removed in vacuo; the residue was purified by chromatography on an Analogix Intelliflash 280™, eluting with a gradient of 9% to 17% ethyl acetate in hexanes. A sample of this product (5.8 of 6.8 g) was dissolved in 30 mL of dichloromethane; 3.0g of NaHCO3 was added, and the mixture was cooled to 0° C. Dess-Martin reagent (5.9 g) was added, and stirring was continued for 2 hours. The solvents were removed in vacuo, and the residue was partitioned between ethyl acetate and water. The organic phase was washed with 1 N aqueous HCl, then brine, and dried over Na2SO4. The organic phase was passed through a plug of silica gel and concentrated in vacuo, giving the titled compound (5.5 g, 71%).

Workup

  1. additionwas added
  2. customThe reaction was quenched by the addition of saturated aqueous NH4Cl
  3. customthe solvents were removed in vacuo
  4. customthe residue was partitioned between ethyl acetate and water
  5. washThe organic phase was washed with 1 N aqueous HCl
  6. dry with materialbrine, and dried over Na2SO4
  7. customThe solvents were removed in vacuo
  8. customthe residue was purified by chromatography on an Analogix IntelliFlash 280™
  9. washeluting with a gradient of 2% to 5% ethyl acetate in hexanes
  10. dissolutionThe product (9.3 g) was dissolved in 75 mL of ethanol
  11. additionpyridinium p-toluenesulfonate (390 mg) was added
  12. stirringthe mixture was stirred at ambient temperature for 1 hour
  13. customThe solvents were removed in vacuo
  14. customthe residue was purified by chromatography on an Analogix Intelliflash 280™
  15. washeluting with a gradient of 9% to 17% ethyl acetate in hexanes
  16. dissolutionA sample of this product (5.8 of 6.8 g) was dissolved in 30 mL of dichloromethane
  17. addition3.0g of NaHCO3 was added
  18. additionDess-Martin reagent (5.9 g) was added
  19. stirringstirring
  20. waitwas continued for 2 hours
  21. customThe solvents were removed in vacuo
  22. customthe residue was partitioned between ethyl acetate and water
  23. washThe organic phase was washed with 1 N aqueous HCl
  24. dry with materialbrine, and dried over Na2SO4
  25. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-971e4e706413450a9e9214471d17df6e
Source dataset
uspto-grants-2013_02
Patent number
US08377913B2

Reaction notes

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