Hydrochloric Acid → N-[2-Formyl-4-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide

HRID 393331

Reaction equation

HRID 393331 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:5][CH:4]=1.C([Li])CCC.CN(C)[CH:25]=[O:26].Cl>>[CH:25]([C:5]1[CH:4]=[C:3]([C:2]([F:16])([F:17])[F:1])[CH:8]=[CH:7][C:6]=1[NH:9][C:10](=[O:15])[C:11]([CH3:12])([CH3:13])[CH3:14])=[O:26]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 2774289N-(4-(trifluoromethyl)phenyl)pivalamideHCID 178418339Butyllithium

Product 1

HCID 21883657N-[2-Formyl-4-(trifluoromethyl)phenyl]-2,2-dimethylpropanamideYield 65.1%

Conditions

Temperature
-78 °C

Procedure

A 1 liter three neck round bottom flask equipped with equalizing addition funnel, magnetic stirer and temperature monitoring device was charged with N-(4-trifluromethylphenyl)-2,2-dimethyl propanamide (10.13 g, 41.4 mmol) and anhydrous tetrahydrafuran (150 mL). The reaction was chilled to −78° C. under nitrogen followed by slow addition of n-butyllithium (50 ml, 2.5 M in hexanes, 124 mmol) over 0.5 hours, such that the temperature of the reaction did not rise above −65° C. The contents were held at −78° C. for one hour, 0° C. for two hours, then chilled back to −78° C. Excess N,N-dimethylformamide (100 mL, 1.37 mol) was added. The contents were warmed to room temperature and stirred for two hours. Aqueous 1 N HCl was added to the reaction until the pH reached 1. The reaction was washed with water (2×200 mL), saturated ammonium chloride solution (2×200 mL), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to afford a yellow solid. The product was purified by flash chromatography (silica gel, 10% ethyl acetate, 90% hexanes) to yield, upon concentration of the appropriate fractions, N-(2-formyl-4-trifluoromethylphenyl)-2,2-dimethylpropanamide as a solid (7.36 g, 65%): mp 69-73° C. 1H HMR (CDCl3/300 MHz) 11.5 (br s, 1H), 9.99 (s, 1H), 8.67 (d, 1H, J=8.8 Hz), 7.94 (d, 1H, J=1.6 Hz), 7.83 (m, 1H), 1.37 (s, 9H). ESHRMS m/z 274.1060 (M+H+, Calc'd 274.1055). Anal. Calc'd for C13H14F3NO2: C, 57.14; H, 5.16; N, 5.13. Found: C, 57.15; H, 5.43; N, 5.01.

Workup

  1. customdid not rise above −65° C
  2. temperaturechilled back to −78° C
  3. temperatureThe contents were warmed to room temperature
  4. washThe reaction was washed with water (2×200 mL), saturated ammonium chloride solution (2×200 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customto afford a yellow solid
  9. customThe product was purified by flash chromatography (silica gel, 10% ethyl acetate, 90% hexanes)

Sources & evidence

ORD record
ord-f901d31880ad46b18b5c49568a333b2b
Source dataset
uspto-grants-2004_10
Patent number
US06806288B1

Linked notes

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