2,4,6-Trimethylaniline → HCID 66899878, compound

HRID 333015Notes

Reaction equation

HRID 333015 reaction equation
[Br:1][C:2]([CH3:7])([CH3:6])[C:3](Br)=[O:4].[CH3:8][C:9]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[C:10]=1[NH2:11].C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]([CH3:7])([CH3:6])[C:3]([NH:11][C:10]1[C:12]([CH3:17])=[CH:13][C:14]([CH3:16])=[CH:15][C:9]=1[CH3:8])=[O:4]

Participants

5

Reactant 3

HCID 69132,4,6-TrimethylanilineHCID 8471TriethylamineHCID 886852-Bromo-2-methylpropionyl bromide

Product 1

HCID 66899878HCID 66899878, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-bromo-2-methylpropanoyl bromide (4.50 g, 19.57 mmol) was added to a mixture of 2,4,6-trimethylaniline (2.41 g, 17.78 mmol), triethylamine (3.60 g, 35.56 mmol), and CH2Cl2 (20 ml) at 0° C. under Ar atmosphere. The cooling bath was removed after the addition was completed, and the reaction mixture was stirred at room temperature for 1.5 hour, after which time the mixture was diluted with CH2Cl2 (20 ml) and added aqueous solution of NH4Cl. After the aqueous phase was separated, the organic layer was washed with brine and dried over anhydrous MgSO4. Filtration and concentration of the filtrate gave 2-bromo-N-mesityl-2-methylpropanamide as a pale yellow solid (5.05 g, 17.78 mmol, 100%). A solution of this amide (284 mg, 1.00 mmol) in dry THF (5 ml) was added to a mixture of sodium hydride (60% in mineral oil, 80 mg, 2.00 mmol), aniline (112 mg, 1.20 mmol) and THF (5 ml), and the resulting mixture was stirred for overnight at room temperature. The mixture was then added an aqueous solution of NH4Cl (15 ml), extracted with ethyl acetate (20 ml×2), and the combined organic layer was washed with brine then dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under vacuum, and the residue was purified by column chromatography on silica (eluent: Hexane/Ethyl acetate=5/1˜4/1) to give the amide as a white solid (255 mg, 0.86 mmol, Y=86%). 1H NMR (300 MHz, CDCl3): δ 8.35 (s, 1H), 7.25-7.17 (m, 2H), 6.84-6.71 (m, 5H), 3.98 (s, 1H), 2.23 (s, 3H), 2.11 (s, 6H), 1.63 (s, 6H). 13C NMR (75 MHz, CDCl3): δ 173.8, 144.5, 136.4, 134.8, 131.0, 129.0, 119.2, 116.2, 58.4, 26.2, 20.8, 18.6. IR: 3341 (m), 3310 (s), 2987 (w), 1666 (s), 1607 (m), 1488 (s), 1376 (m), 1318 (m), 1264 (m), 1210 (m), 1162 (m), 850 (m), 749 (s), 696 (m) cm−1. HRMS Calc'd for C19H24N2O: 297.1967. Meas: 297.1956.

Workup

  1. customThe cooling bath was removed
  2. additionafter the addition
  3. additionafter which time the mixture was diluted with CH2Cl2 (20 ml)
  4. additionadded aqueous solution of NH4Cl
  5. customAfter the aqueous phase was separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationFiltration and concentration of the filtrate

Sources & evidence

ORD record
ord-900024fc0d4f4a0db7aff4794963903b
Source dataset
uspto-grants-2014_11
Patent number
US08877936B2

Reaction notes

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