Isobutyraldehyde → 2,4-dimethyl-N-(2-methylpropyl)aniline

HRID 1746393Notes

Reaction equation

HRID 1746393 reaction equation
C([O-])=O.[NH4+].[CH3:5][C:6]1[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][C:7]=1[NH2:8].[CH:14](=O)[CH:15]([CH3:17])[CH3:16]>C(O)(C)C.[Pd]>[CH3:5][C:6]1[CH:12]=[C:11]([CH3:13])[CH:10]=[CH:9][C:7]=1[NH:8][CH2:14][CH:15]([CH3:17])[CH3:16]

Participants

6

Reactant 3

HCID 6561IsobutyraldehydeHCID 72502,4-DimethylanilineHCID 2723923Ammonium formate

Product 1

HCID 284223892,4-dimethyl-N-(2-methylpropyl)anilineYield 84.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 3776IsopropanolSolvent2×

Procedure

An aqueous solution of ammonium formate (3.15 g, 50.0 mmol, 10 mL) was diluted with isopropanol (80 mL) and added to palladium on carbon 10% wet (1.064 g, 10.00 mmol) under nitrogen. A solution of 2,4-dimethylaniline (1.212 g, 10 mmol) and isobutyraldehyde (1.004 mL, 11.00 mmol) in isopropanol (3 mL) was added and the mixture was stirred for 1 h. The mixture was filtered through celite, the celite cake washed with isopropanol and combined liquid phases concentrated in vacuo. The residue (1.8 g) was purified using a pre-conditioned aminopropyl solid phase extraction cartridge (NH2 SPE) (20 g) using methanol as an eluent. The methanolic organic phase was concentrated under vacuo to give a second residue which was further purified on a Biotage Flashmaster II using silica (Si) 10 g/mmol using a 0-100% dichloromethane-cyclohexane gradient over 40 mins. The fractions containing the expected product were combined and concentrated in vacuo to give the desired product 1.5 g as a yellow oil.

Workup

  1. filtrationThe mixture was filtered through celite
  2. washthe celite cake washed with isopropanol
  3. concentrationconcentrated in vacuo
  4. customThe residue (1.8 g) was purified
  5. extractiona pre-conditioned aminopropyl solid phase extraction cartridge (NH2 SPE) (20 g)
  6. concentrationThe methanolic organic phase was concentrated under vacuo
  7. customto give a second residue which
  8. customwas further purified on a Biotage Flashmaster II
  9. customover 40 mins
  10. additionThe fractions containing the expected product
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7b2cb31305ff486f88cb58ba234a06fc
Source dataset
uspto-grants-2015_10
Patent number
US09150508B2

Reaction notes

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