L-Tartaric acid → HCID 178526011, compound

HRID 1960042Notes

Reaction equation

HRID 1960042 reaction equation
C([O-])=O.[NH4+].[CH2:5]([O:12][CH2:13][CH2:14][C@H:15]1[CH2:20][CH2:19][C@H:18]([C@H:21]2[CH2:25][CH2:24][CH2:23][N:22]2[C@@H](C2C=CC=CC=2)CO)[CH2:17][CH2:16]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C(OCC[C@H]1CC[C@H]([C@H]2CCCN2)CC1)C1C=CC=CC=1.[C:56]([OH:65])(=[O:64])[C@@H:57]([C@H:59]([C:61]([OH:63])=[O:62])[OH:60])[OH:58]>CO.[Pd].CCO>[C:56]([OH:65])(=[O:64])[CH:57]([CH:59]([C:61]([OH:63])=[O:62])[OH:60])[OH:58].[CH2:5]([O:12][CH2:13][CH2:14][C@H:15]1[CH2:20][CH2:19][C@H:18]([C@H:21]2[CH2:25][CH2:24][CH2:23][NH:22]2)[CH2:17][CH2:16]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

8

Reactant 4

HCID 444305L-Tartaric acidHCID 2723923Ammonium formateHCID 178420423HCID 178420423, compoundHCID 178521074HCID 178521074, compound

Product 1

HCID 178526011HCID 178526011, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

To a stirred mixture of anhydrous ammonium formate (15.8 g, 0.25 mol) and trans-(S)-2-{(R)-2-[4-(benzyloxyethyl)cyclohexyl]pyrrolidin-1-yl}-2-phenylethanol (20.5 g, 0.050 mol) in MeOH (200 mL) is added 10% palladium on carbon (1.00 g), and the resulting mixture is stirred under nitrogen atmosphere at room temperature for 2 hours and then at 35° C. for 3 hours. The reaction mixture is filtered, and the filtrate is concentrated. The crude residue is dissolved with 1N HCl and extracted with ether to remove phenethylalcohol. The water layer is neutrized by addition of 2.5 N NaOH and extracted with CH2Cl2. The combined organic layer is washed with brine, dried over magnesium sulfate, filtered and concentrated to give crude trans-(R)-2-[4-(benzyloxyethyl)cyclohexyl]pyrrolidine. To the mixture of crude trans-(R)-2-[4-(benzyloxyethyl)cyclohexyl]pyrrolidine in EtOH (65 mL), L-tartaric acid (7.60 g, 0.050 mol) is added. The resulting mixture is warmed to 60° C., then cooled slowly to room temperature. The precipitate is filtered and rinsed with additional EtOH to afford trans-(R)-2-[4-(benzyloxyethyl)cyclohexyl]pyrrolidine tartaric acid salt as off-white crystal. The tartaric acid salt is dissolved in 1N NaOH aq. and extracted with CH2Cl2, and the organic layer is dried over magnesium sulfate, filtered, and evaporated to afford pure trans-(R)-2-[4-(benzyloxyethyl)cyclohexyl]pyrrolidine.

Workup

  1. waitat 35° C. for 3 hours
  2. filtrationThe reaction mixture is filtered
  3. concentrationthe filtrate is concentrated
  4. dissolutionThe crude residue is dissolved with 1N HCl
  5. extractionextracted with ether
  6. customto remove phenethylalcohol
  7. additionThe water layer is neutrized by addition of 2.5 N NaOH
  8. extractionextracted with CH2Cl2
  9. washThe combined organic layer is washed with brine
  10. dry with materialdried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give crude trans-(R)-2-[4-(benzyloxyethyl)cyclohexyl]pyrrolidine
  14. additionis added
  15. temperatureThe resulting mixture is warmed to 60° C.
  16. temperaturecooled slowly to room temperature
  17. filtrationThe precipitate is filtered
  18. washrinsed with additional EtOH

Sources & evidence

ORD record
ord-bf99ad267bf3442192b4e6271601c462
Source dataset
uspto-grants-2013_04
Patent number
US08410275B2

Reaction notes

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