Hydrogen Peroxide → (2R,3R,4R,alphaR)-alpha-2-Propenyl-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-methanol

HRID 747024Notes

Reaction equation

HRID 747024 reaction equation
[CH2:1]([Mg]Br)[CH:2]=[CH2:3].ClB([C@H]1C[C@H]2C[C@H](C2(C)C)[C@@H]1C)[C@H]1C[C@H]2C[C@H](C2(C)C)[C@@H]1C.[F:28][C:29]([F:58])([F:57])[C:30]1[CH:31]=[C:32]([C@H:40]([O:42][C@@H:43]2[C@@H:48]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C@H:47]([CH:55]=[O:56])[CH2:46][CH2:45][O:44]2)[CH3:41])[CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1.C([O-])(=O)C.[Na+].OO>C(OCC)C>[CH2:3]([C@H:55]([C@@H:47]1[CH2:46][CH2:45][O:44][C@H:43]([O:42][C@@H:40]([C:32]2[CH:31]=[C:30]([C:29]([F:57])([F:28])[F:58])[CH:35]=[C:34]([C:36]([F:39])([F:37])[F:38])[CH:33]=2)[CH3:41])[C@H:48]1[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[OH:56])[CH:2]=[CH2:1]

Participants

7

Reactant 5

HCID 784Hydrogen PeroxideHCID 517045Sodium AcetateHCID 9923113Chlorobis((1S,2R,3S,5S)-2,6,6-trimethylbicyclo(3.1.1)hept-3-yl)boraneHCID 86601738(2R,3R,4R)-2-[(1R)-1-(3,5-bis(trifluoromethyl)phenyl)ethoxy]-3-phenyl-tetrahydropyran-4-carbaldehydeHCID 178455850HCID 178455850, compound

Product 1

HCID 86606917(2R,3R,4R,alphaR)-alpha-2-Propenyl-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-methanolYield 78.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

Allylmagnesium bromide (15.4 mL, 15.4 mmol) was slowly added to a stirred, cooled −40° C. solution of chlorobis[(1S,2R,3S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]borane (5.91 g, 18 mmol) in diethyl ether (20 mL). The mixture was warmed to room temperature and stirred for 1 hour before cooling to −78° C. (2R,3R,4R)-2-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-carboxaldehyde (WO 00/56727A1; 5.5 g, 12.3 mmol) in diethyl ether (10 mL) was slowly added and the mixture was stirred at −78° C. for 1.5 hours. The mixture was warmed to room temperature and stirred for a further 1.5 hours. The mixture was cooled to −78° C. and aqueous sodium acetate (3M, 20 mL) then aqueous hydrogen peroxide (31% wt, 10 mL) were added. The mixture was allowed to warm to room temperature and stirred overnight. The layers were separated and the aqueous layer was extracted with ethyl acetate (2×150 mL). The combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/hexane (90:10), to give the title compound as a yellow oil (4.7 g, 78%).

Workup

  1. additionwas slowly added
  2. stirringthe mixture was stirred at −78° C. for 1.5 hours
  3. temperatureThe mixture was warmed to room temperature
  4. stirringstirred for a further 1.5 hours
  5. temperatureThe mixture was cooled to −78° C.
  6. temperatureto warm to room temperature
  7. stirringstirred overnight
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (2×150 mL)
  10. dry with materialThe combined organic fractions were dried (MgSO4)
  11. customthe solvent was evaporated under reduced pressure
  12. customThe residue was purified by column chromatography on silica gel
  13. washeluting with EtOAc/hexane (90:10)

Sources & evidence

ORD record
ord-d3a2d2450c3a452e8ff18320f8970011
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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