N-Methoxy-N-methylpropionamide → HCID 71059804, compound

HRID 241449Notes

Reaction equation

HRID 241449 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[CH3:12].C([Li])CCC.CON(C)[C:21](=[O:24])[CH2:22][CH3:23]>C1COCC1>[CH3:12][C:3]1[CH:4]=[C:5]([C:8]([F:11])([F:10])[F:9])[CH:6]=[CH:7][C:2]=1[C:21](=[O:24])[CH2:22][CH3:23]

Participants

5

Reactant 3

HCID 11344007N-Methoxy-N-methylpropionamideHCID 227541411-Bromo-2-methyl-4-(trifluoromethyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 71059804HCID 71059804, compoundYield 82.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-71 °C

Procedure

Cool a solution of 1-bromo-2-methyl-4-(trifluoromethyl)benzene (2.00 g, 8.367 mmol) and THF (17 mL) to −71° C., and then add n-butyl lithium (2.5 M in hexanes, 9.204 mmol, 3.681 mL) over 5 minutes. Stir the mixture for 15 minutes at −71° C. Add N-methoxy-N-methylpropanamide (0.980 g, 8.367 mmol) to the mixture drop-wise over 3-4 minutes keeping temperature below −65° C. Continue to stir the solution at −71° C. for 15-20 minutes; then warm the solution to room temperature. Stir at room temperature for 40 minutes. Quench the reaction with a saturated ammonium chloride aqueous solution. Extract the aqueous layer with Et2O. Wash the combined organic extracts with water and brine. Dry the mixture over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Purify the residue by flash chromatography (40 g RediSep® column) eluting with a gradient of 0-40% DCM/pentane to give the title compound as a colorless oil (1.490 g, 82% yield). 1H NMR (399.80 MHz, d6-DMSO) δ 7.84 (d, J=7.8 Hz, 1H), 7.64-7.61 (m, 2H), 2.93 (q, J=7.1 Hz, 2H), 2.39 (s, 3H), 1.03 (t, J=7.2 Hz, 3H).

Workup

  1. customtemperature below −65° C
  2. stirringto stir the solution at −71° C. for 15-20 minutes
  3. temperaturethen warm the solution to room temperature
  4. stirringStir at room temperature for 40 minutes
  5. customQuench
  6. customthe reaction with a saturated ammonium chloride aqueous solution
  7. extractionExtract the aqueous layer with Et2O
  8. washWash the combined organic extracts with water and brine
  9. dry with materialDry the mixture over sodium sulfate
  10. filtrationfilter
  11. customcollect the filtrate
  12. concentrationand concentrate the filtrate under reduced pressure
  13. customPurify the residue by flash chromatography (40 g RediSep® column)
  14. washeluting with a gradient of 0-40% DCM/pentane

Sources & evidence

ORD record
ord-66e21231850549e7a10caefb851f2d35
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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