Acetyl chloride → HCID 19791664, compound

HRID 1655327Notes

Reaction equation

HRID 1655327 reaction equation
[CH3:1][CH:2]([CH3:24])[CH2:3][CH2:4][CH:5]([NH:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)[CH:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[OH:7].[OH-].[Na+].[C:27]([Cl:30])(=O)[CH3:28].[H-].[Al+3].[Li+].[H-].[H-].[H-]>CCOCC.C1C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[ClH:30].[ClH:30].[CH2:27]([N:14]([CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1)[CH:5]([CH2:4][CH2:3][CH:2]([CH3:24])[CH3:1])[CH:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[OH:7])[CH3:28]

Participants

9

Reactant 4

HCID 6367Acetyl chlorideHCID 14798Sodium HydroxideHCID 1283085-Methyl-1-phenyl-2-{[3-(piperidin-1-yl)propyl]amino}hexan-1-olHCID 21226445Aluminium lithium hydride

Product 1

HCID 19791664HCID 19791664, compound

Reagents, catalysts & solvents 4

HCID 241BenzeneSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a cooled mixture of (1RS,2SR)-5-methyl-1-phenyl-2-(3-piperidinopropylamino)hexan-1-ol (821 mg, 2.47 mmol) in ether (36 ml) and a 10% NaOH aqueous solution (15 ml) was added dropwise a solution of acetyl chloride (0.21 g, 2.7 mmol) in benzene. The organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain an N-acetylated product (IRνmaxneat : 1620 cm-1) of the starting material. To a cooled solution of such compound in tetrahydrofuran (12.4 ml) was added lithium aluminum hydride (0.47 g) and the reaction mixture was refluxed for 3 hours. Ethyl acetate was added with cooling to the mixture to consume excess lithium aluminum hydride and the mixture was then poured into an aqueous saturated sodium sulfate solution. The organic layer was separated by decantation, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform/methanol =25/1) to give a free base of the title compound. To a solution of the compound in ethanol was added in excess 6N-HCl in EtOH and the mixture was concentrated under reduced pressure. The residue was crystallized by treatment with ether, followed by recrystallization from ethanol-ethyl acetate to obtain 510 mg of the title compound as white crystals (yield: 48%).

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography
  6. customto obtain an N-acetylated product (IRνmaxneat : 1620 cm-1) of the starting material
  7. temperaturethe reaction mixture was refluxed for 3 hours
  8. temperaturewith cooling to the mixture
  9. customto consume excess lithium aluminum hydride
  10. additionthe mixture was then poured into an aqueous saturated sodium sulfate solution
  11. customThe organic layer was separated by decantation
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (eluent: chloroform/methanol =25/1)

Sources & evidence

ORD record
ord-652ed7ddf457467889111efcfecb996e
Source dataset
uspto-grants-1993_10
Patent number
US05250546

Reaction notes

Loading…