Acetyl chloride → 1-{4-[2-(2,4-Dichlorophenoxy)anilino]piperidin-1-yl}ethan-1-one

HRID 1642234Notes

Reaction equation

HRID 1642234 reaction equation
[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(N(CC)CC)C.[C:30](Cl)(=[O:32])[CH3:31]>C(Cl)Cl>[Cl:1][C:2]1[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][CH:12]1[CH2:17][CH2:16][N:15]([C:30](=[O:32])[CH3:31])[CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 57550297N-[2-(2,4-Dichlorophenoxy)phenyl]piperidin-4-amine

Product 1

HCID 159530471-{4-[2-(2,4-Dichlorophenoxy)anilino]piperidin-1-yl}ethan-1-oneYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cooled solution of [2-(2,4-dichlorophenoxy)phenyl]piperidin-4-ylamine (AMR01040, 132 mg, 0.39 mmol) in dry DCM (5 mL) were added triethylamine (0.137 mL, 0.98 mmol) and acetyl chloride (0.031 mL, 0.43 mmol). The reaction mixture was stirred at room temperature until completion by TLC (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-{4-[2-(2,4-dichlorophenoxy)phenylamino]piperidin-1-yl}ethanone (95.3 mg, 64%) as a white solid after, mp 145-146° C. Rf: 0.22 (EtOAc) LC/MS (APCI) tr=1.44 min, m/z 381.29 (63), 379.34 (M++H, 100) HPLC tr=3.10 min (99.31%) 1H NMR (270 MHz, CDCl3) δ 1.36 (2H, m, CH2), 2.06 (2H, m, CH2), 2.08 (3H, s, CH3), 2.89 (1H, m), 3.20 (1H, m), 3.53 (1H, m), 3.74 (1H, m), 4.05 (1H, m), 4.37 (1H, m), 6.63 (1H, m, ArH), 6.74 (1H, dd, J=7.9, 1.5 Hz, ArH), 6.75 (1H, dd, J=8.2, 1.5 Hz, ArH), 6.80 (1H, d, J=8.9 Hz, ArH), 7.03 (1H, m, ArH), 7.12 (1H, dd, J=8.9, 2.5 Hz, ArH) and 7.43 (1H, d, J=2.5 Hz, ArH). Anal. Calcd. for C19H20Cl2N2O2: C, 60.17; H, 5.32; N, 7.39. Found: C, 59.90; H, 5.47; N, 7.13%.

Workup

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

Sources & evidence

ORD record
ord-3fb6c809bc094ec2b7473414b5c4d904
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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