4-[2-(4-Chlorophenoxy)phenylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester → N-[2-(4-Chlorophenoxy)phenyl]piperidine-4-carboxamide

HRID 1642229Notes

Reaction equation

HRID 1642229 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:30])[NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[CH2:10][CH2:9]1)=O)(C)(C)C>Cl.O1CCOCC1>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([O:22][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[NH:15][C:14]([CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[O:30])=[CH:24][CH:25]=1

Participants

4

Reactant 1

HCID 575503174-[2-(4-Chlorophenoxy)phenylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57550281N-[2-(4-Chlorophenoxy)phenyl]piperidine-4-carboxamideYield 74.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-[2-(4-chlorophenoxy)phenylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester (AMR01031, 410 mg, 0.95 mmol) in 4M HCl in dioxane (2 mL) was stirred at room temperature for 2 h. The resulting solution was concentrated under vacuum and the residue was dissolved in DCM, washed with 1M NaOH (1×20 mL), water and brine. The organic layer was dried (MgSO4), filtered and evaporated to give piperidine-4-carboxylic acid [2-(4-chlorophenoxy)phenyl]amide (233 mg, 74%) as a white solid (mp 138-140° C. from hexane/EtOAc), which was used in the next step without further purification. Rf: 0.11 (DCM/methanol 4:1 plus 3 drops of triethylamine) 1H NMR (270 MHz, CDCl3) δ 1.62 (2H, m, CH2), 1.83 (3H, m, CH2+NH), 2.35 (1H, tt, J=11.6, 3.7 Hz, CH), 2.62 (2H, br t, CH2), 3.20 (2H, br d, J=12.3 Hz, CH2), 6.80 (1H, td, ArH), 6.92 (2H, AA′BB′, ArH), 6.98 (1H, td, ArH), 7.11 (1H, td, ArH), 7.29 (1H, AA′BB′, ArH), 7.71 (1H, br s, NHCO) and 8.41 (1H, br d, J=7.9 Hz, ArH).

Workup

  1. concentrationThe resulting solution was concentrated under vacuum
  2. dissolutionthe residue was dissolved in DCM
  3. washwashed with 1M NaOH (1×20 mL), water and brine
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-35c59c24dd504575abb01df6bb9e084f
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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