Pyridine → 1-Benzoyl-N-[2-(4-chlorophenoxy)phenyl]piperidine-4-carboxamide

HRID 1642230Notes

Reaction equation

HRID 1642230 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][C:14]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[O:15])=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:30](Cl)(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([O:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[NH:13][C:14]([CH:16]2[CH2:17][CH2:18][N:19]([C:30](=[O:37])[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:20][CH2:21]2)=[O:15])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 7412Benzoyl chlorideHCID 57550281N-[2-(4-Chlorophenoxy)phenyl]piperidine-4-carboxamide

Product 1

HCID 159529411-Benzoyl-N-[2-(4-chlorophenoxy)phenyl]piperidine-4-carboxamideYield 83.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of piperidine-4-carboxylic acid [2-(4-chlorophenoxy)phenyl]amide (AMR01033, 73 mg, 0.22 mmol) in dry DCM (6 mL) were added pyridine (0.036 mL, 0.44 mmol) and benzoyl chloride (0.038 mL, 0.33 mmol). The reaction mixture was stirred at room temperature until TLC showed consumption of starting material (1 h), and quenched with saturated NaHCO3. The resulting solution was extracted with DCM (3×20 mL), and the combined organic layers were washed with water, 1M HCl (3×20 mL) and brine, dried (MgSO4), filtered and evaporated. Flash chromatography on silica gel of the crude product using hexane to EtOAc gradient as eluent gave 1-benzoylpiperidine-4-carboxylic acid [2-(4-chlorophenoxy)phenyl]amide (80 mg, 83%) as a white solid, mp 158-160° C. Rf: 0.48 (EtOAc) LC/MS (APCI) tr=1.05 min, m/z 437.33 (45), 435.38 (M++H, 100) HPLC tr=2.551 min (98.36%) 1H NMR (270 MHz, CDCl3) δ 1.82 (4H, m, 2CH2), 2.51 (1H, tt, CH), 2.98 (2H, n, CH2), 3.85 (1H, m, ½CH2), 4.71 (1H, m, ½CH2), 6.82 (1H, dd, J=8.2, 1.5 Hz, ArH), 6.93 (2H, AA′BB′, ArH), 7.02 (1H, td, ArH), 7.13 (1H, td, ArH), 7.31 (1H, AA′BB′, ArH), 7.39 (5H, s, ArH,), 7.70 (1H, br s, NH) and 8.39 (1H, dd, J=8.2, 1.5 Hz, ArH). Anal. Calcd. for C25H23ClN2O3: C, 69.04; H, 5.33; N, 6.44. Found: C, 68.9; H, 5.33; N, 6.37%.

Workup

  1. customconsumption of starting material (1 h)
  2. customquenched with saturated NaHCO3
  3. extractionThe resulting solution was extracted with DCM (3×20 mL)
  4. washthe combined organic layers were washed with water, 1M HCl (3×20 mL) and brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-b06dd98f88d3479389bb333d603b8b3b
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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