Pyridine → 1-Benzoylpiperidine-4-carboxylic acid [2-(2,4-dichloro-phenoxy)phenyl]amide

HRID 1642232Notes

Reaction equation

HRID 1642232 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)=[O:13].N1C=CC=CC=1.[C:31](Cl)(=[O:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([CH:14]1[CH2:19][CH2:18][N:17]([C:31](=[O:38])[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:16][CH2:15]1)=[O:13]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7412Benzoyl chlorideHCID 57550293N-[2-(2,4-Dichlorophenoxy)phenyl]piperidine-4-carboxamide

Product 1

HCID 159529401-Benzoylpiperidine-4-carboxylic acid [2-(2,4-dichloro-phenoxy)phenyl]amideYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)phenyl]-amide (AMR01038, 100 mg, 0.274 mmol) in dry DCM (10 mL) were added pyridine (0.044 mL, 0.548 mmol) and benzoyl chloride (0.047 mL, 0.411 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-(2,4-dichloro-phenoxy)phenyl]amide (98 mg, 76%) as a white solid, mp 176-177° C. Rf: 0.17 (hexane/EtOAc 1:1) LC/MS (APCI) tr=1.10 min, m/z 471.26 (58), 469.31 (M++H, 100) HPLC tr=2.88 min (99.48%) 1H NMR (270 MHz, CDCl3) δ 1.85 (4H, m, 2CH2), 2.55 (1H, tt, CH), 3.01 (2H, m, CH2), 3.89 (1H, m, ½CH2), 4.74 (1H, m, ½CH2), 6.72 (1H, dd, J=8.2, 1.5 Hz, ArH), 6.95 (1H, d, J=8.6 Hz, ArH), 7.01 (1H, td, ArH), 7.14 (1H, td, ArH), 7.22 (1H, dd, J=8.6, 2.5 Hz, ArH), 7.39 (5H, s, ArH), 7.49 (1H, d, J=2.5 Hz, ArH), 7.78 (1H, br s, NH) and 8.38 (1H, br d, J=8.2, ArH). Anal. Calcd. for C25H22Cl2N2O3: C, 63.97; H, 4.72; N, 5.97. Found: C, 64.10; H, 4.83; N, 5.88%.

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-4c0bc59bb2ba4f55ac3ba79bacf0450f
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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