Dimethyl Sulfoxide → {1-[(4-(2-Pyridyloxy)phenyl)methyl](4-piperidyl)}[4-(trifluoromethyl)phenyl]methanol

HRID 2245308Notes

Reaction equation

HRID 2245308 reaction equation
Cl.[F:2][C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1C1(CO)CCNCC1)([F:5])[F:4].[CH:20]([N:23]([CH2:27][CH3:28])[CH:24]([CH3:26])C)([CH3:22])C.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[O:35][C:36]1[CH:41]=[CH:40]C(CCl)=[CH:38][CH:37]=1.[C:44](=[O:47])([O-])[O-].[Na+].[Na+].[CH3:50]S(C)=O>>[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[O:35][C:36]1[CH:37]=[CH:38][C:28]([CH2:27][N:23]2[CH2:20][CH2:22][CH:50]([CH:44]([C:9]3[CH:8]=[CH:7][C:6]([C:3]([F:2])([F:4])[F:5])=[CH:11][CH:10]=3)[OH:47])[CH2:26][CH2:24]2)=[CH:40][CH:41]=1

Participants

6

Reactant 5

HCID 679Dimethyl SulfoxideHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 22292927(4-(2-Pyridyloxy)phenyl)methyl chlorideHCID 1317266924-(Trifluoromethylphenyl)-4-piperidylmethanol, hydrochloride salt

Product 1

HCID 11554030{1-[(4-(2-Pyridyloxy)phenyl)methyl](4-piperidyl)}[4-(trifluoromethyl)phenyl]methanol

Procedure

A solution of 6.1 grams (0.021 mole) of 4-(trifluoromethylphenyl)-4-piperidylmethanol, hydrochloride salt in 31 mL of DMSO was stirred, and 10.7 grams (0.083 mole) of N,N-diisopropylethylamine was added. Upon completion of addition, the reaction mixture was stirred for 10 minutes, and was then added to the 5.0 grams (0.023 mole) of (4-(2-pyridyloxy)phenyl)methyl chloride that was prepared in Step B of this Example. Upon completion of addition, the reaction mixture was stirred at ambient temperature for 16 hours. After this time, the reaction mixture was treated with aqueous 10% sodium carbonate and extracted with ethyl acetate. The ethyl acetate layer was washed with water, then with an aqueous solution saturated with sodium chloride. The ethyl acetate layer was dried with sodium sulfate, filtered, and concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using mixtures of acetone and methylene chloride as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 4.2 grams of the subject compound. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionUpon completion of addition
  2. additionUpon completion of addition
  3. stirringthe reaction mixture was stirred at ambient temperature for 16 hours
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with water
  6. dry with materialThe ethyl acetate layer was dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure to a residue
  9. customThe residue was purified with column chromatography on silica gel using mixtures of acetone and methylene chloride as eluants
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a693b99ebee540a387a5232bdef12810
Source dataset
uspto-grants-2010_03
Patent number
US07683070B2

Reaction notes

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