Tetrahydrofuran → HCID 11002155, compound

HRID 618453Notes

Reaction equation

HRID 618453 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22].C(N(CC)CC)C.C1C[O:33][CH2:32]C1>>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:32](=[O:33])[NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 199606-Amino-1-hexanolHCID 784611-Benzylpiperidin-4-ol

Product 1

HCID 11002155HCID 11002155, compoundYield 100%

Conditions

Temperature
50 °C

Procedure

A stirred suspension of N,N'-carbonyldiimidazole (3.24 g, 20 mmol) in The (40 mL) was warmed up to 50° C., and a solution of 1-benzyl-4-hydroxypiperidine (3.82 g, 20 mmol) in THF (17 mL) was added dropwise over 10 min. Stirring was continued for 2 hrs. at room temperature (RT), and a solution of 6-aminohexanol (3.50 g, 30 mmol) and triethylamine (3.04 g, 30 mmol) in THF (40 mL) was added dropwise over 10 min. When the reaction mixture turned cloudy, the rate of stirring was increased, and a clear solution was obtained within 20-30 min. The mixture was refluxed for 2 hrs., concentrated in vacuo, and the residue was partitioned between ether (70 mL) and water (35 mL). An alternative partitioning between ethyl acetate and water was equally effective. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated to give the title compound (6.68 g, yield 100%) as a light, yellowish oil. TLC (chloroform-5% methanol) showed a single spot at Rf 0.5; 1H NMR (300 MHz, CDCl3) δ1.37 (m, 4H, CH2), 1.47-1.61 (m, 4H, CH2), 1.67 (m, 2H, CH2, piperidine ring axial protons), 1.88 (m, 2H, CH2, piperidine ring equatorial protons), 2.22 (t, J=9 Hz, 2H, CH--N--CH, piperidine ring axial protons), 2.69 (m, 2H, CH--N--CH, piperidine ring eq. protons), 3.16 (q, J=6.5 Hz, 2H, CH2 --NH), 3.49 (s, 2H, CH2 --Ph), 3.62 (t, J=6.5 Hz, 2H, CH2 --O), 4.66 (m, 1H, CH--O), 4.73 (t, J=6 Hz, 1H, NH), 7.23-733 (m, 5H, Ar--H).

Workup

  1. stirringthe rate of stirring
  2. temperaturewas increased
  3. customa clear solution was obtained within 20-30 min
  4. temperatureThe mixture was refluxed for 2 hrs
  5. concentration, concentrated in vacuo
  6. customthe residue was partitioned between ether (70 mL) and water (35 mL)
  7. customAn alternative partitioning between ethyl acetate and water
  8. washThe organic layer was washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-0560a661e7cb497a9e5ef97e377d9726
Source dataset
uspto-grants-1999_09
Patent number
US05952506

Reaction notes

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