Reaktion #328631

Reaktionsgleichung

1-bromo-2-methyl-4-(trifluoromethyl)benzene

n-butyl lithium

N-methoxy-N-methylpropanamide

→

title compound

Ausbeute 82.4%

1-[2-Methyl-4-(trifluoromethyl)phenyl]propan-1-one

Ausbeute 82.4%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigetemperature below −65° C
2. 2
   workup.STIRRINGto stir the solution at −71° C. for 15-20 minutes
3. 3
   Temperaturthen warm the solution to room temperature
4. 4
   workup.STIRRINGStir at room temperature for 40 minutes
5. 5
   SonstigeQuench
6. 6
   Sonstigethe reaction with a saturated ammonium chloride aqueous solution
7. 7
   ExtraktionExtract the aqueous layer with Et2O
8. 8
   WaschenWash the combined organic extracts with water and brine
9. 9
   TrocknenDry the mixture over sodium sulfate
10. 10
    Filtrationfilter
11. 11
    Sonstigecollect the filtrate
12. 12
    Einengenand concentrate the filtrate under reduced pressure
13. 13
    SonstigePurify the residue by flash chromatography (40 g RediSep® column)
14. 14
    Wascheneluting with a gradient of 0-40% DCM/pentane

Vorschrift

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).

Quelle