Methanone, (1-fluorocyclopropyl)(4-fluorophenyl)- (9CI) synthesis

Yield:103543-82-4 47%

Reaction Conditions:

with sodium hexamethyldisilazane in tetrahydrofuran at 0 - 20;

Steps:

19 (1-Fluorocyclopropyl)(4-fluorophenyl)methanone

Reference Example 19
(1-Fluorocyclopropyl)(4-fluorophenyl)methanone
A tetrahydrofuran solution (3.97 mL, 4.33 mmol) of 1.09 M sodium bis(trimethylsilyl)amide was added to a THF (8.0 mL) solution of the compound obtained in Reference Example 18 (861 mg, 3.94 mmol) at 0° C. over 30 minutes, and the mixture was stirred at room temperature for 2.5 hours.
A saturated aqueous solution of ammonium chloride and water were added to the reaction mixture, and the mixture was subjected to extraction twice with hexane.
The organic layer thus obtained was washed with water and brine, and then was dried over anhydrous sodium sulfate.
The solvent was distilled off under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5, v/v) to give the title compound (336 mg, yield: 47%).
¹H-NMR (500 MHz, CDCl₃) δ ppm:
8.10-8.05 (2H, m), 7.15 (2H, t, J=9 Hz), 1.61-1.54 (2H, m), 1.52-1.45 (2H, m).

References:

US2013/217733,2013,A1 Location in patent:Paragraph 0192; 0193; 01494; 0195