Benzaldehyde → HCID 17956592, compound

HRID 2223719Notes

Reaction equation

HRID 2223719 reaction equation
[CH2:1]([C:8]1([OH:14])[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[O-]S([O-])(=O)=O.[Mg+2].CC(C)(O)[C:31]#[N:32].[H-].[H-].[H-].[H-].[Li+].[Al+3]>CN1CCCC1=O.C1COCC1>[NH2:32][CH2:31][CH:15]([N:11]1[CH2:12][CH2:13][C:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)([OH:14])[CH2:9][CH2:10]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 5

HCID 240BenzaldehydeHCID 6406Acetone CyanohydrinHCID 24083Sulfuric acid magnesium salt (1:1)HCID 981524-Benzyl-4-piperidinolHCID 21226445Aluminium lithium hydride

Product 1

HCID 17956592HCID 17956592, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

To a suspension of 4-benzyl-piperidin-4-ol (1.0 g, 5.2 mmol), benzaldehyde (0.83 g, 7.8 mmol) and MgSO4 (0.31 g, 2.6 mmol) in 1-methyl-2-pyrrolidone (5 mL) is added acetone cyanohydrine (0.45 g, 5.2 mmol). The reaction mixture is heated at 50° C. for 2 h, then cooled to room temperature and quenched with ice (20 g) and sat. NaHCO3 (50 mL). The aqueous phase is extracted with Et2O (3×100 mL), the combined organic extracts are washed with sat. NaCl (20 mL), dried (Na2SO4), filtered and evaporated. The residue is dissolved in THF (20 mL) and added to a suspension of LiAlH4 (1.1 g, 27.6 mmol) in THF (80 mL) at 0° C. The reaction mixture is stirred for 15 h at room temperature and quenched with EtOAc (250 mL), MeOH (20 mL) and sat. NaHCO3 (5 mL). The precipitate is filtered off, washed with MeOH (20 mL) and the filtrate evaporated. Purification by preparative HPLC provides the title compound.

Workup

  1. temperaturecooled to room temperature
  2. customquenched with ice (20 g) and sat. NaHCO3 (50 mL)
  3. extractionThe aqueous phase is extracted with Et2O (3×100 mL)
  4. washthe combined organic extracts are washed with sat. NaCl (20 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue is dissolved in THF (20 mL)
  9. customquenched with EtOAc (250 mL), MeOH (20 mL) and sat. NaHCO3 (5 mL)
  10. filtrationThe precipitate is filtered off
  11. washwashed with MeOH (20 mL)
  12. customthe filtrate evaporated
  13. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-318cc3a9954542c4bd222663c520cbbb
Source dataset
uspto-grants-2008_05
Patent number
US07375227B2

Reaction notes

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