Hydrochloride methanol → (3RS, 4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid methyl ester

HRID 2191101Notes

Reaction equation

HRID 2191101 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=[O:15])[CH:10]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:25]O>CO>[CH3:25][O:15][C:14]([CH:11]1[CH2:12][CH2:13][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH:10]1[C:17]1[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=1)=[O:16]

Participants

4

Reactant 2

HCID 21893726Hydrochloride methanol2×HCID 68479302(3RS,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid2×

Product 1

HCID 68517588(3RS, 4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
76 °C

Procedure

In a 500 ml round bottom flask with a magnetic stirring bar 3 g (9 mmol) (3RS, 4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid (SM050/4A) were suspended in 100 ml methanol. 50 mL 1.25 N HCl/MeOH was added and the mixture was stirred over night at reflux (76° C.). Another 50 mL 1.25 N HCl/MeOH was added and the reaction mixture was continued to reflux for 24 h. The solvent was removed by evaporation and the brown residue was diluted with 200 mL Na2CO3 aq. sat. and 5 mL 4 N NaOH aq. The mixture was extracted with 3 portions of 200 mL ethyl acetate. The combined organic layers were washed with 150 mL brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography on silica eluting with ethyl acetate/heptane to yield after evaporation of the product containing fractions 2.74 g (88%) of the title compound as light yellow viscous oil. MS (m/e): 344.2 [(M+H)+].

Workup

  1. temperatureto reflux for 24 h
  2. customThe solvent was removed by evaporation
  3. additionthe brown residue was diluted with 200 mL Na2CO3 aq. sat.
  4. extraction5 mL 4 N NaOH aq. The mixture was extracted with 3 portions of 200 mL ethyl acetate
  5. washThe combined organic layers were washed with 150 mL brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography on silica eluting with ethyl acetate/heptane
  10. customto yield
  11. customafter evaporation of the product
  12. additioncontaining fractions 2.74 g (88%) of the title compound as light yellow viscous oil

Sources & evidence

ORD record
ord-102db7b75afe40cc87cccc86ac6dbf23
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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