Hydrochloric Acid → 4-(4-Chlorophenyl)-3,3-dimethylpiperidin-4-ol

HRID 2069167Notes

Reaction equation

HRID 2069167 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:23])[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][C:9]2([CH3:22])[CH3:21])=[CH:4][CH:3]=1.Cl>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:23])[CH2:13][CH2:12][NH:11][CH2:10][C:9]2([CH3:21])[CH3:22])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 593412124-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 231311434-(4-Chlorophenyl)-3,3-dimethylpiperidin-4-olYield 101%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of (±)-tert-butyl 4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carboxylate (93.7 g, 0.276 mol) in dioxane (100 mL) was treated with 4 M HCl solution in dioxane (275 mL, 1.1 mol). The resulting mixture was stirred at room temperature for four hours. After this time, the mixture was concentrated in vacuo, and then concentrated 3× from methylene chloride (200 mL) to remove residual HCl. The resulting residue was stirred in 1 M NaOH (500 mL), and the resulting suspension was extracted 4× with 500 mL of ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, and concentrated in vacuo to yield the title compound (66.8 g, quantitative yield) as a solid.

Workup

  1. concentrationAfter this time, the mixture was concentrated in vacuo
  2. concentrationconcentrated 3× from methylene chloride (200 mL)
  3. customto remove residual HCl
  4. stirringThe resulting residue was stirred in 1 M NaOH (500 mL)
  5. extractionthe resulting suspension was extracted 4× with 500 mL of ethyl acetate
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fcaf523153d84d389f67b23f0adf3859
Source dataset
uspto-grants-2012_10
Patent number
US08299098B2

Reaction notes

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