Hydrochloric Acid → 1-(tert-Butoxycarbonyl)-4-(3-chlorophenyl)piperidine-4-carboxylic acid

HRID 625070Notes

Reaction equation

HRID 625070 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2([C:21]#N)[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Cl.[OH-:24].[Na+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.[OH2:41]>O1CCOCC1>[C:17]([O:16][C:14]([N:11]1[CH2:12][CH2:13][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)([C:21]([OH:41])=[O:24])[CH2:9][CH2:10]1)=[O:15])([CH3:20])([CH3:19])[CH3:18]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 49760302tert-Butyl 4-(3-chlorophenyl)-4-cyanopiperidine-1-carboxylate

Product 1

HCID 450744981-(tert-Butoxycarbonyl)-4-(3-chlorophenyl)piperidine-4-carboxylic acidYield 75.56%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

tert-Butyl 4-(3-chlorophenyl)-4-cyanopiperidine-1-carboxylate (5.91 g, 18.42 mmol) was dissolved in concentrated HCl (153.5 ml, 1842 mmol). The reaction mixture stirred at reflux over a weekend. The reaction mixture was cooled to room temperature and washed with ether. The aqueous portion was concentrated on a rotary evaporator, and the solids were dried on a high vacuum line. The solids were dissolved in H2O (35 mL), 10% NaOH (29.47 g, 73.69 mmol), and dioxane (30 mL). Solid Boc2O (4.222 g, 19.34 mmol) was added, and reaction mixture stirred at room temperature overnight (14 hours). The reaction mixture was diluted with H2O and washed with ether. The aqueous portion was acidified with solid KHSO4, then extracted with DCM. The combined extracts were dried (Na2SO4), filtered, and concentrated to give 1-(tert-butoxycarbonyl)-4-(3-chlorophenyl)piperidine-4-carboxylic acid (4.73 g, 75.56% yield) as a white powder. HPLC>98%. LC/MS (APCI−) m/z 338 [M−H]−.

Workup

  1. temperatureat reflux over a weekend
  2. washwashed with ether
  3. concentrationThe aqueous portion was concentrated on a rotary evaporator
  4. customthe solids were dried on a high vacuum line
  5. dissolutionThe solids were dissolved in H2O (35 mL)
  6. customreaction mixture
  7. stirringstirred at room temperature overnight (14 hours)
  8. washwashed with ether
  9. extractionextracted with DCM
  10. dry with materialThe combined extracts were dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-1df8b1d6fa8a42acaba6f178472cafb1
Source dataset
uspto-grants-2016_04
Patent number
US09303040B2

Reaction notes

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