Hydrochloric Acid → 1-(Tert-butoxycarbonyl)-4-(4-chlorophenyl)piperidine-4-carboxylic acid

HRID 2104231Notes

Reaction equation

HRID 2104231 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:15]([OH:17])=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[C:18]([O-:21])([O-])=[O:19].[K+].[K+].Cl>O>[C:6]([O:21][C:18]([N:12]1[CH2:11][CH2:10][C:9]([C:6]2[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][CH:5]=2)([C:15]([OH:17])=[O:16])[CH2:14][CH2:13]1)=[O:19])([CH3:9])([CH3:7])[CH3:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 690497324-(4-Chloro-phenyl)-piperidine-4-carboxylic acid hydrochloride

Product 1

HCID 248288571-(Tert-butoxycarbonyl)-4-(4-chlorophenyl)piperidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A sample of crude 4-(4-chloro-phenyl)-piperidine-4-carboxylic acid hydrochloride (5 mmol, 1 equiv) and 15 g of K2CO3 (113 mmol, 22.6 equiv) was diluted in 50 mL H2O. To the resultant solution was added a solution of 7.4 g BOC20 (34.1 mmol, ˜7 equiv) in 50 mLp-dioxane and the reaction mixture was stirred overnight under N2 atmosphere. The pH was adjusted to ˜4 with 1M HCl and allowed to stir for about 0.5 hour. The reaction mixture was concentrated under vacuum, and the remaining solution was extracted with 2×50 mL EtOAc. The combined organic extracts were dried under vacuum to yield 4-(4-chloro-phenyl)-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester. The crude material was used without further purification for the next step: MS (ES) M−H expected=338.8, found=338.1.

Workup

  1. stirringto stir for about 0.5 hour
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. extractionthe remaining solution was extracted with 2×50 mL EtOAc
  4. customThe combined organic extracts were dried under vacuum

Sources & evidence

ORD record
ord-4c02b82ce9464db8985752374cd7268e
Source dataset
uspto-grants-2009_08
Patent number
US07576218B2

Reaction notes

Loading…