Water → 2-[4-(2-methoxyphenyl)piperidin-1-yl]-N-(m-tolyl)acetamide

HRID 490167Notes

Reaction equation

HRID 490167 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C([N:18]([CH2:22][CH3:23])[CH:19]([CH3:21])[CH3:20])(C)C.[OH2:24]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]1[CH2:14][CH2:13][N:12]([CH2:23][C:22]([NH:18][C:19]2[CH:20]=[CH:8][CH:3]=[C:4]([CH3:5])[CH:21]=2)=[O:24])[CH2:11][CH2:10]1

Participants

5

Reactant 3

HCID 962WaterHCID 81531DiisopropylethylamineHCID 5447384-(2-Methoxyphenyl)piperidine

Product 1

HCID 104723232-[4-(2-methoxyphenyl)piperidin-1-yl]-N-(m-tolyl)acetamideYield 52.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

4-(2-Methoxyphenyl)piperidine (200 mg, 1 mmol), the product from Example 1A (228 mg, 1 mmol) and N,N-diisopropylethylamine (0.185 mL, 1.1 mmol) in toluene (8 mL) were stirred at 60° C. for 18 hours. The reaction mixture was poured into water (30 mL) and extracted with ethyl acetate (30 mL). The organic layer was washed with brine (2×30 mL), dried over MgSO4, filtered and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (elution with dichloromethane:methanol, 9.5:0.5) to provide the title compound 177 mg (52.3%). 1H NMR (300 MHz, DMSO-d6) δ 1.71 (m, 4H), 2.28 (m, 5H), 2.89 (m, 1H), 2.96 (m, 2H), 3.13 (s, 2H), 3.78 (s, 3H), 6.91 (m, 3H), 7.20 (m, 3H), 7.45 (m, 2H), 8.69 (s, 1H); MS (DCI/NH3) m/e 339 (M+H)+. Anal. calcd for C21H26N2O2: C, 74.52; H, 7.74; N, 8.28. Found: C, 74.23, H, 7.71, N, 8.26.

Workup

  1. extractionextracted with ethyl acetate (30 mL)
  2. washThe organic layer was washed with brine (2×30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (elution with dichloromethane:methanol, 9.5:0.5)

Sources & evidence

ORD record
ord-9c76198f09d942d39ea4008b77b8573b
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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