Sodium Hydroxide → 2-Benzyl-3-[4-(4-chlorophenyl)-4-fluoropiperidin-1-yl]propionic acid Hydrochloride

HRID 537207Notes

Reaction equation

HRID 537207 reaction equation
Cl.[CH2:2]([CH:9]([CH2:14][N:15]1[CH2:20][CH2:19][C:18]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)([F:21])[CH2:17][CH2:16]1)[C:10]([O:12]C)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[OH-].[Na+]>CO>[ClH:28].[CH2:2]([CH:9]([CH2:14][N:15]1[CH2:16][CH2:17][C:18]([C:22]2[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=2)([F:21])[CH2:19][CH2:20]1)[C:10]([OH:12])=[O:11])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67460614Methyl 2-Benzyl-3-[4-(4-Chlorophenyl)-4-fluoropiperidin-1-yl]propionate Hydrochloride

Product 1

HCID 674618232-Benzyl-3-[4-(4-chlorophenyl)-4-fluoropiperidin-1-yl]propionic acid HydrochlorideYield 55%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of methyl 2-benzyl-3-[4-(4-chlorophenyl)-4-fluoropiperidin-1-yl]propionate hydrochloride in methanol (2.5 mL) was added 50% aqueous sodium hydroxide solution (1 mL) and the resulting solution heated to reflux under N2 for 14 hours. After this time the reaction was cooled and concentrated. The residue was treated with 2N hydrochloric acid (6 mL) and the mixture stirred for 1 hr. The reaction was then extracted with 2-butanone (3×10 mL) and the extracts dried over magnesium sulfate, filtered and concentrated. The oily residue was re-dissolved in EtOAc (10 mL) re-filtered and concentrated. The residue was then re-dissolved in 2-butanone and concentrated to afford a yellow foam. This material was dried under high vacuum for 16 hours to afford a 55% yield of the title compound as a yellow foam.

Workup

  1. temperaturethe resulting solution heated
  2. temperatureto reflux under N2 for 14 hours
  3. temperatureAfter this time the reaction was cooled
  4. concentrationconcentrated
  5. additionThe residue was treated with 2N hydrochloric acid (6 mL)
  6. extractionThe reaction was then extracted with 2-butanone (3×10 mL)
  7. dry with materialthe extracts dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe oily residue was re-dissolved in EtOAc (10 mL)
  11. filtrationre-filtered
  12. concentrationconcentrated
  13. dissolutionThe residue was then re-dissolved in 2-butanone
  14. concentrationconcentrated
  15. customto afford a yellow foam
  16. customThis material was dried under high vacuum for 16 hours

Sources & evidence

ORD record
ord-e8f89834554e4e80a5fa8fca8a89a73b
Source dataset
uspto-grants-2014_10
Patent number
US08859777B2

Reaction notes

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