Ammonium Chloride → (1R)-1-((2R,3R,4R)-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy}-tetrahydro-3-phenyl-2H-pyran-4-yl)-1,3-propanediol

HRID 747026Notes

Reaction equation

HRID 747026 reaction equation
[CH2:1]([C@H:4]([C@@H:6]1[CH2:11][CH2:10][O:9][C@H:8]([O:12][C@@H:13]([C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:25]([F:28])([F:27])[F:26])[CH:16]=2)[CH3:14])[C@H:7]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[OH:5])[CH:2]=C.[BH4-].[Na+].[Cl-].[NH4+].ClCCl.C[OH:43]>>[F:22][C:21]([F:24])([F:23])[C:19]1[CH:20]=[C:15]([C@H:13]([O:12][C@@H:8]2[C@@H:7]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C@H:6]([C@H:4]([OH:5])[CH2:1][CH2:2][OH:43])[CH2:11][CH2:10][O:9]2)[CH3:14])[CH:16]=[C:17]([C:25]([F:28])([F:27])[F:26])[CH:18]=1

Participants

5

Reactant 4

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 21226129Dichloromethane methanolHCID 86606917(2R,3R,4R,alphaR)-alpha-2-Propenyl-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-methanol

Product 1

HCID 86606919(1R)-1-((2R,3R,4R)-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy}-tetrahydro-3-phenyl-2H-pyran-4-yl)-1,3-propanediolYield 50%

Conditions

Temperature
-78 °C

Procedure

(2R,3R,4R,αR)-α-2-Propenyl-2-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-tetrahydro-3-phenyl-2H-pyran-4-methanol (Description 31; 1.0 g, 2 mmol) was dissolved in dichloromethane/methanol (1:1, 30 mL), cooled to −78° C. and purged with nitrogen and then oxygen. Ozone was bubbled through the mixture for 15-20 minutes, until a blue coloration persisted. The mixture was purged with oxygen, then nitrogen, warmed to 0° C. and sodium borohydride (0.3 g, 8 mmol) was added in portions. The mixture was stirred at 0° C. for 30 minutes, aqueous ammonium chloride (10%, 40 mL) was added and the mixture was extracted with dichloromethane (2×75 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 (50:50) to give the title compound as a colorless oil (0.5 g, 50%).

Workup

  1. custompurged with nitrogen
  2. customOzone was bubbled through the mixture for 15-20 minutes, until a blue coloration
  3. customThe mixture was purged with oxygen
  4. temperaturenitrogen, warmed to 0° C.
  5. extractionthe mixture was extracted with dichloromethane (2×75 mL)
  6. dry with materialThe combined organic fractions were dried (MgSO4)
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel
  9. washeluting with EtOAc/hexane (50:50)

Sources & evidence

ORD record
ord-e711f60ae38640aabb091506b256d8f3
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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