Potassium Carbonate → N-[1-(6-Hydroxy-benzofuran-3-ylmethyl)-piperidin-4-yl]-acetamide

HRID 1947499Notes

Reaction equation

HRID 1947499 reaction equation
[C:1]([NH:4][CH:5]1[CH2:10][CH2:9][NH:8][CH2:7][CH2:6]1)(=[O:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].Cl[CH2:18][C:19]1[C:23]2[CH:24]=[CH:25][C:26]([O:28]C(=O)C)=[CH:27][C:22]=2[O:21][CH:20]=1>CC#N>[OH:28][C:26]1[CH:25]=[CH:24][C:23]2[C:19]([CH2:18][N:8]3[CH2:9][CH2:10][CH:5]([NH:4][C:1](=[O:3])[CH3:2])[CH2:6][CH2:7]3)=[CH:20][O:21][C:22]=2[CH:27]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 14451564-AcetamidopiperidineHCID 59577463Acetic acid 3-chloromethyl-benzofuran-6-yl ester

Product 1

HCID 59577711N-[1-(6-Hydroxy-benzofuran-3-ylmethyl)-piperidin-4-yl]-acetamide

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Conditions

Temperature
50 °C

Procedure

To a solution of 4-acetamidopiperidine (429 mg, 3.00 mmol) and K2CO3 (1.14 g, 8.25 mmol) in MeCN (5 mL) was added a solution of acetic acid 3-chloromethyl-benzofuran-6-yl ester (450 mg, 2.0 mmol) in MeCN (5 mL). The reaction mixture was further diluted with MeCN (10 mL) and heated (50° C., 15 h). The solvent was removed in vacuo and the remaining residue was suspended in 5-10% CH3OH in water and enough concentrated acetic acid was added until all solids were dissolved (pH ˜7-8). The solution was slowly basified using 4 N KOH until precipitate was observed. The precipitate was filtered and rinsed with water. The pH of the mother liquor was further adjusted (4 N KOH and concentrated acetic acid) to produce additional precipitate, which was filtered and rinsed with water. This process of pH adjustment and solid filtration was repeated until no additional precipitate was observed. The precipitate was combined and dried in vacuo to provide the title compound as an off white solid (419 mg, 73%). MS (ESI): mass calcd. for C16H20N2O3, 288.15; m/z found, 289.1 [M+H]+. 1H NMR (400 MHz, DMSO-d6): 9.44 (s, 1H), 7.69 (d, J=7.6, 1H), 7.63 (s, 1H), 7.47 (d, J=8.4, 1H), 6.86 (d, J=2.0, 1H), 6.72 (dd, J=8.4, 2.1, 1H), 3.56-3.44 (m, 3H), 2.86-2.74 (m, 2H), 1.99 (t, J=10.6, 2H), 1.76 (s, 3H), 1.74-1.62 (m, 2H), 1.43-1.27 (m, 2H).

Workup

  1. customThe solvent was removed in vacuo
  2. additionenough concentrated acetic acid was added until all solids
  3. dissolutionwere dissolved (pH ˜7-8)
  4. filtrationThe precipitate was filtered
  5. washrinsed with water
  6. customto produce additional precipitate, which
  7. filtrationwas filtered
  8. washrinsed with water
  9. filtrationThis process of pH adjustment and solid filtration
  10. customdried in vacuo

Sources & evidence

ORD record
ord-b12f920f0b6a4819b62b0dcc90a700b5
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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