Benzoyl chloride → N-(1-Benzoylpiperidin-4-yl)-2-(2,4-dichlorophenoxy)benzamide

HRID 1642249Notes

Reaction equation

HRID 1642249 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:19]=[CH:18][CH:17]=[CH:16][C:6]=1[C:7]([NH:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)=[O:8].C(N(CC)CC)C.[C:32](Cl)(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(Cl)Cl>[C:32]([N:13]1[CH2:14][CH2:15][CH:10]([NH:9][C:7](=[O:8])[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[O:4][C:3]2[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:2]=2[Cl:1])[CH2:11][CH2:12]1)(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 575503182-(2,4-Dichlorophenoxy)-N-(piperidin-4-yl)benzamide

Product 1

HCID 15952348N-(1-Benzoylpiperidin-4-yl)-2-(2,4-dichlorophenoxy)benzamideYield 80.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of 4-[2-(2,4-dichloro-phenoxy)-N-piperidin-4-ylbenzamide (AMR01077, 100 mg, 0.274 mmol) in dry DCM (5 mL) were added triethylamine (0.2 mL, 1.37 mmol) and benzoyl chloride (0.038 mL, 0.33 mmol). The reaction mixture was stirred at room temperature until completion by TLC (1.5 h), and quenched with saturated NaHCO3. The organic solution was evaporated to dryness and the oil obtained was purified by column chromatography using DCM/MeOH 95:5 as eluent. Further purification was carried out by treating a DCM solution of the obtained compound with trisamine scavenger (100 mg) for 2 h. The scavenger was filtered off, and the solvent evaporated to give N-(1-benzoylpiperidin-4-yl)-2-(2,4-dichlorophenoxy)benzamide (103 mg, 80%) as a white solid, mp 63-66° C. Rf: 0.15 (hexane/AcOEt 4:6) LC/MS (APCI) tr=4.94 min, m/z 471.32 (65), 469.31 (M++H, 100). HPLC tr=2.35 min (98.01%) 1H NMR (270 MHz, CDCl3) δ 1.35 (2H, m, CH2), 1.55 (2H, m, CH2), 1.76 (6H, m, 3CH2), 2.00 (2H, m, CH2), 2.87 (2H, m, CH2), 3.17 (1H, m, ½CH2), 3.87 (1H, br t, ½CH2), 4.19 (1H, m, CH), 4.43 (1H, m, ½CH2) 6.79 (1H, d, J=8.6 Hz, ArH), 7.21 (1H, dd, J=8.9, 2.5 Hz, ArH), 7.25 (1H, m ArH), 7.35 (1H, br d, NH), 7.50 (1H, d, J=2.5 Hz, ArH) and 8.17 (1H, dd, J=7.9, 1.7 Hz, ArH). 13C NMR (270 MHz, CDCl3) δ 23.81, 29.36, 32.26, 33.17 (CH2), 39.60 (CH), 40.78 (CH2), 43.70 (CH), 47.79 (CH2), 118.00, 120.65, 124.43, 124.88, 126.21, 128.57, 130.85, 130.87, 132.74, 133.06, 148.97, 153.09 (ArC), 163.63 and 174.71 (C═O).

Workup

  1. customquenched with saturated NaHCO3
  2. customThe organic solution was evaporated to dryness
  3. customthe oil obtained
  4. customwas purified by column chromatography
  5. customFurther purification
  6. additionby treating a DCM solution of the obtained compound with trisamine scavenger (100 mg) for 2 h
  7. filtrationThe scavenger was filtered off
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-361d7f1ca36f43a0864c6ccb4fdaa989
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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