Diisopropylamine → (3RS)-3-(2-Methoxy-5-methylphenyl)-N,N-bis(1-methylethyl)-3-phenylpropan-1-amine

HRID 1769805Notes

Reaction equation

HRID 1769805 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[CH:10]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:11][C:12](O)=O.S(Cl)(Cl)=O.[CH:25]([NH:28][CH:29]([CH3:31])[CH3:30])([CH3:27])[CH3:26].[H-].[Al+3].[Li+].[H-].[H-].[H-]>ClCCl.CCOCC>[CH:25]([N:28]([CH2:12][CH2:11][CH:10]([C:4]1[CH:5]=[C:6]([CH3:9])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH:29]([CH3:31])[CH3:30])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 24386Thionyl ChlorideHCID 34683223-(2-Methoxy-5-methylphenyl)-3-phenylpropanoic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 9923998(3RS)-3-(2-Methoxy-5-methylphenyl)-N,N-bis(1-methylethyl)-3-phenylpropan-1-amine

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

3-(2-Methoxy-5-methylphenyl)-3-phenylpropionic acid (12.8 g, 0.05 mol) (J. D. Simpson & H. Stehphen, J. Chem. Soc. 1956 1382) and thionyl chloride (50 ml) are heated on a water bath for 3 h. The excess of thionyl chloride is distilled off under reduced pressure. The remaining crude 3-(2-methoxy-5-methylphenyl)3-phenylpropionyl chloride is dissolved in 50 ml of dichloromethane and added dropwise to a stirred solution of diisopropylamine (20.2 g, 0.20 mol) in 200 ml of dichloromethane at about 0° C. The solution is left for 2 h, the solvent is distilled off and the remaining material is treated with water. The solid product consisting of N,N-diisopropyl-3-(2-methoxy-5-methylphenyl)-3-phenylpropionamide is filtered off, dried and added in small portions to a stirred suspension of lithium aluminium hydride (6.0 g, 0.16 mol) in dry ether (700 ml). The mixture is refluxed for 2 days. Excess of hydride is destroyed by the careful addition of water, the ether layer is separated and dried with anhydrous sodium sulfate. After filtration the solution is added to a solution of excess fumaric acid in ether. The precipitated salt is collected and crystallized from 2-propanol. The hydrogen fumarate melts at 176° C.

Workup

  1. distillationThe excess of thionyl chloride is distilled off under reduced pressure
  2. dissolutionThe remaining crude 3-(2-methoxy-5-methylphenyl)3-phenylpropionyl chloride is dissolved in 50 ml of dichloromethane
  3. distillationthe solvent is distilled off
  4. additionthe remaining material is treated with water
  5. filtrationis filtered off
  6. customdried
  7. temperatureThe mixture is refluxed for 2 days
  8. customExcess of hydride is destroyed by the careful addition of water
  9. customthe ether layer is separated
  10. dry with materialdried with anhydrous sodium sulfate
  11. filtrationAfter filtration the solution
  12. additionis added to a solution of excess fumaric acid in ether
  13. customThe precipitated salt is collected
  14. customcrystallized from 2-propanol

Sources & evidence

ORD record
ord-b7941396825d4ebba181c22b2714e3e7
Source dataset
uspto-grants-1995_01
Patent number
US05382600

Reaction notes

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