Hydrochloric Acid → 4-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]-1-methyl-1,2,3,6-tetrahydropyridine

HRID 2216375Notes

Reaction equation

HRID 2216375 reaction equation
[CH2:1]([C:8]1[C:13]([C:14]2(O)[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)=[CH:12][CH:11]=[C:10]([N:22]2[CH2:26][C@@H:25]([O:27][CH3:28])[C@H:24]([OH:29])[CH2:23]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH2:1]([C:8]1[C:13]([C:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH:15]=2)=[CH:12][CH:11]=[C:10]([N:22]2[CH2:26][C@@H:25]([O:27][CH3:28])[C@H:24]([OH:29])[CH2:23]2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 587007554-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]-1-methyl-4-piperidinol

Product 1

HCID 587007534-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]-1-methyl-1,2,3,6-tetrahydropyridineYield 17%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 63.0 mg of 4-[2-Benzyl-6-[(3R,4R)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridyl]-1-methyl-4-piperidinol (Example 3) and 1.5 ml of 1 M acetic acid solution of hydrogen chloride was stirred at 70° C. for 9 hours. The reaction mixture was neutralized with an aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and the solvent was removed. To the residue were added 50 mg of potassium carbonate and 1 ml of methanol, followed by stirring at room temperature for 1 hour. NH-silica gel was added to the reaction mixture and the solvent was removed. It was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate, to give 10.2 mg of the title compound.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was removed
  5. additionTo the residue were added 50 mg of potassium carbonate and 1 ml of methanol
  6. stirringby stirring at room temperature for 1 hour
  7. additionNH-silica gel was added to the reaction mixture
  8. customthe solvent was removed
  9. customIt was purified by NH-silica gel column chromatography with 5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-ae16cf669519457e9e7631dff0f6873a
Source dataset
uspto-grants-2006_09
Patent number
US07112593B2

Reaction notes

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