Hydrochloric Acid → 5-[(3-Trifluoromethylphenethyl)-methylamino]-2-(3,5-dimethoxyphenyl)-2-isopropylvaleronitrile

HRID 1073249Notes

Reaction equation

HRID 1073249 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([CH:19]([CH3:21])[CH3:20])([CH2:14][CH2:15][CH2:16][NH:17][CH3:18])[C:12]#[N:13])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(C(C1C=C(OC)C=C(OC)C=1)C#N)(C)C.CC(NCCCCl)=O.[H-].[Na+].Cl.[F:49][C:50]([F:61])([F:60])[C:51]1[CH:52]=[C:53]([CH2:57][CH:58]=O)[CH:54]=[CH:55][CH:56]=1>[Pd].C1(C)C=CC=CC=1>[F:49][C:50]([F:61])([F:60])[C:51]1[CH:52]=[C:53]([CH:54]=[CH:55][CH:56]=1)[CH2:57][CH2:58][N:17]([CH3:18])[CH2:16][CH2:15][CH2:14][C:11]([C:5]1[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)([CH:19]([CH3:21])[CH3:20])[C:12]#[N:13]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 3361051N-(3-chloropropyl)acetamideHCID 14183624alpha-Isopropyl-3,5-dimethoxyphenylacetonitrileHCID 212463392-(3-(Trifluoromethyl)phenyl)acetaldehydeHCID 221584772-(3,5-Dimethoxyphenyl)-2-isopropyl-5-methylaminovaleronitrile

Product 1

HCID 139233825-[(3-Trifluoromethylphenethyl)-methylamino]-2-(3,5-dimethoxyphenyl)-2-isopropylvaleronitrileYield 86.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 29.0 g (0.1 mole) of 2-(3,5-dimethoxyphenyl)-2-isopropyl-5-methylaminovaleronitrile (prepared by reacting α-isopropyl-3,5-dimethoxyphenylacetonitrile and 3-methylformamido-1-chloropropane in the presence of sodium hydride and then eliminating the formyl group by means of hydrochloric acid) and 18.8 g (0.1 mole) of 3-trifluoromethylphenylacetaldehyde was reduced catalytically with 400 mg of 5% strength palladium on carbon in 100 ml of toluene under atmospheric pressure at from 25 to 30° C. for 20 hours. After the catalyst had been removed, the toluene solution was washed several times with water and dried with potassium carbonate, after which the toluene was distilled off. The residue was dissolved in isopropanol, and ethanolic hydrochloric acid was added. Crystallization from isopropanol gave 39.9 g (80%) of 5-[(3-trifluoromethylphenethyl)-methylamino]-2-(3,5-dimethoxyphenyl)-2-isopropylvaleronitrile of melting point 136°-138° C.

Workup

  1. customprepared
  2. customAfter the catalyst had been removed
  3. washthe toluene solution was washed several times with water
  4. dry with materialdried with potassium carbonate
  5. distillationafter which the toluene was distilled off
  6. dissolutionThe residue was dissolved in isopropanol
  7. additionethanolic hydrochloric acid was added
  8. customCrystallization from isopropanol

Sources & evidence

ORD record
ord-1899f7c3a7d84a91ace19e0da60b5f40
Source dataset
uspto-grants-1990_11
Patent number
US04968717

Reaction notes

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