p-Toluenesulfonic acid → 3-(Tert-butyl)-5-(1,1-dimethoxyethyl)-2-methoxyaniline

HRID 1296015Notes

Reaction equation

HRID 1296015 reaction equation
[CH:1]([O:6][CH3:7])([O:4][CH3:5])OC.[C:8]1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:19][C:20]1[CH:21]=[C:22](C(=O)C)[CH:23]=[C:24]([C:28]([CH3:31])([CH3:30])[CH3:29])[C:25]=1[O:26][CH3:27]>CO>[C:28]([C:24]1[C:25]([O:26][CH3:27])=[C:20]([CH:21]=[C:22]([C:1]([O:4][CH3:5])([O:6][CH3:7])[CH3:8])[CH:23]=1)[NH2:19])([CH3:30])([CH3:29])[CH3:31]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 22929815HCID 22929815, compound

Product 1

HCID 229300733-(Tert-butyl)-5-(1,1-dimethoxyethyl)-2-methoxyaniline

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Trimethyl orthoformate (20 ml), p-toluenesulfonic acid (0.5 g, 1.9 mmol) and 3A-molecular sieves (4 g) were added to a solution of 1-[3-amino-5-(tert-butyl)-4-methoxyphenyl]-1-ethanone (4 g, 19 mmol) in methanol (20 ml) and the mixture was stirred at room temperature for 13 hours. The reaction mixture was filtered through celite and the solvent was distilled off under reduced pressure. Ethyl acetate was added to the residue, the mixture was washed with brine, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to yield 5.2 g of 3-(tert-butyl)-5-(1,1-dimethoxyethyl)-2-methoxyaniline as a crude product. Acetone (1.7 ml, 22 mmol), acetic acid (3.2 ml, 56 mmol) and 3A-molecular sieves (2 g) were added to a solution of the compound (5.2 g, 19 mmol) in methanol (6 ml) and the mixture was stirred at room temperature for 3 hours. Sodium cyanoborohydride (1.1 g, 17 mmol) was added to the reaction mixture prior to stirring at room temperature for 2 hours. Ethyl acetate was added to the reaction mixture, washing was performed with saturated sodium hydrogencarbonate water and brine in that order, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and then the residue was purified by silica gel column chromatography (solvent: n-hexane-ethyl acetate) to yield the title compound (1.0 g) as a light yellow oil.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. distillationthe solvent was distilled off under reduced pressure
  3. additionEthyl acetate was added to the residue
  4. washthe mixture was washed with brine
  5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-a15d1dcf873a48cc906b50b32d5c8168
Source dataset
uspto-grants-2007_07
Patent number
US07244730B2

Reaction notes

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