Isopropanol → [3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutyl]-methanol

HRID 1241506Notes

Reaction equation

HRID 1241506 reaction equation
OC(C(F)(F)F)=O.C([O:15][CH2:16][CH:17]1[CH2:20][CH:19]([C:21]2[CH:32]=[CH:31][C:24]([CH2:25][N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:23][CH:22]=2)[CH2:18]1)C1C=CC=CC=1.CC(O)C>C(O)C.[Pd]>[N:26]1([CH2:25][C:24]2[CH:31]=[CH:32][C:21]([CH:19]3[CH2:18][CH:17]([CH2:16][OH:15])[CH2:20]3)=[CH:22][CH:23]=2)[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

5

Reactant 2

HCID 3776IsopropanolHCID 866000091-[4-(3-benzyloxymethyl-cyclobutyl)-benzyl]-pyrrolidine TFA salt

Product 1

HCID 21934866[3-(4-Pyrrolidin-1-ylmethyl-phenyl)-cyclobutyl]-methanolYield 79%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a stirring solution of crude 1-[4-(3-benzyloxymethyl-cyclobutyl)-benzyl]-pyrrolidine TFA salt prepared above (61.5 mmol) in 250 mL of ethyl alcohol was added palladium black (4.0 g, 20% by wt). The Parr bottle was then pressurized with H2 to 45 psi. After complete consumption of starting material as evident by LRMS the reaction vessel was evacuated (removal of H2 gas), then the reaction was filtered through a plug of Celite, and concentrated under reduced pressure. The residual was diluted with CH2Cl2 and washed with a saturated solution of NaHCO3. The aqueous layer was back extracted with 3:1 CHCl3:iPrOH. The organic layers were dried over magnesium sulfate, filtered through a fritted funnel and concentrated under reduced pressure. Purification of this material was accomplished by flash chromatography, using a Biotage column 75 large, eluting with a gradient of 2% MeOH/CH2Cl2 w/0.2% NH4OH, through 20% MeOH/CH2Cl2 w/0.2% NH4OH. The product containing fractions were collected and concentrated, 13C NMR revealed the presence of TFA. The product was free based by reaction with aqueous K2CO3, and extracted with 3:1 CHCl3:iPrOH to yield the title compound (11.9 g, 79% yield) as a colorless oil and a mixture of cis:trans isomers.

Workup

  1. customAfter complete consumption of starting material as evident by LRMS the reaction vessel
  2. customwas evacuated
  3. custom(removal of H2 gas)
  4. filtrationthe reaction was filtered through a plug of Celite
  5. concentrationconcentrated under reduced pressure
  6. additionThe residual was diluted with CH2Cl2
  7. washwashed with a saturated solution of NaHCO3
  8. extractionThe aqueous layer was back extracted with 3:1 CHCl3
  9. dry with materialThe organic layers were dried over magnesium sulfate
  10. filtrationfiltered through a fritted funnel
  11. concentrationconcentrated under reduced pressure
  12. customPurification of this material
  13. washeluting with a gradient of 2% MeOH/CH2Cl2
  14. additionThe product containing fractions
  15. customwere collected
  16. concentrationconcentrated
  17. customThe product was free based by reaction with aqueous K2CO3
  18. extractionextracted with 3:1 CHCl3

Sources & evidence

ORD record
ord-c6176e54b233495ca859ad8e3e913e7d
Source dataset
uspto-grants-2006_10
Patent number
US07115600B2

Reaction notes

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