1-Pentanone, 1-[3-(trifluoromethyl)phenyl]- synthesis

Yield:1705-17-5 72 %

Reaction Conditions:

in tetrahydrofuran at 0 - 20;Inert atmosphere;

Steps:

1-[3-(Trifluoromethyl)phenyl]pentan-1-one (4b)

To a solution of amide 3 (1.00 g; 4.29 mmol) in dry THF (10 mL), 2.5 M solution of butyllithium (1.80 ml; 4.50 mmol) was introduced at 0 °C under an inertatmosphere of argon. Then, the resulting reaction mixture was stirred at roomtemperature for 4 h. Subsequently, the pH of the reaction mixture was adjustedto approximately 2 by 1 M hydrochloric acid, water (20 mL) was added and theresulting phases were separated. The aqueous phase was then extracted with MTBE(3 × 15 mL), the combined organic layers were washed with brine (20 mL), driedwith magnesium sulfate, and concentrated by drying the product under reducedpressure. The resultant residue was purified by column chromatography (eluenthexane:toluene 1:1, v:v) to give the ketone 4b (712 mg, 72% yield) as a yellowish liquid.¹HNMR (400 MHz, CDCl₃): 0.96 (t, 3H, CH₃, J = 7.3Hz), 1.42 (dq, 2H, CH₂, J = 14.7, 7.4 Hz), 1.73 (dt, 2H, CH₂,J = 15.0, 7.5 Hz), 3.00 (t, 2H, CH₂, J = 7.5 Hz), 7.60(t, 1H, CH, J = 7.8 Hz), 7.80 (d, 1H, CH, J = 7.8 Hz), 8.14(d, 1H, CH, J = 7.8 Hz), 8.20 (s, 1H, CH). ¹⁹F NMR(282 MHz, CDCl₃): -62.86 (s, 3F, CF₃). ¹³C NMR(101 MHz, CDCl₃): 13.87 (s, 1C, CH₃), 22.35 (s, 1C, CH₂),26.14 (s, 1C, CH₂), 38.36 (s, 1C, CH₂), 123.70 (q, 1C, CF₃,J = 272.5 Hz), 124.82 (q, 1C, CH, J = 3.8 Hz), 129.21 (s, 1C,CH), 129.23 (q, 1C, CH, J = 3.6 Hz), 131.14 (q, 1C, C, J = 32.8Hz), 131.15 (s, 1C, CH), 137.50 (s, 1C, C), 198.98 (s, 1C, CO).

References:

Dob?íková;Javorská;Pa?kan;Spálovská;Trembulaková;Herciková;Kucha?;Kozmík;Kohout;Setni?ka [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2023,vol. 291,art. no. 122320]