Yield:19561-95-6 68%

Reaction Conditions:

with trifluoroacetic anhydride at 20;

Steps:

4.1 Step 1: l-(4-(2-Chloroethoxy)phenyl)-2-phenylethan-l-one:

Phenyl acetic acid (2.6 g, 19 mmol) was suspended in trifluoroacetic anhydride (11 mL, 76 mmol). Chloroethyoxylbenzene (2.7 mL, 19 mmol) was added to the stirred suspension dropwise. The resulting mixture was allowed to stir overnight at room temperature. The reaction was quenched with 40% aqueous sodium hydroxide solution and then extracted with ethyl acetate (2 x 15 mL). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by chromatography on silica gel (ethyl acetate/hexane) to afford 3.56 g (68%) of the desired product as a yellow solid. NMR (400 (0772) MHz, CDCI₃) δ 7.93 (d, J = 6.8 Hz, 2H), 7.22 (m, 5H), 6.87 (d, J = 6.9 Hz, 2H), 4.21 (t, J= 5.8 Hz, 2H), 4.17 (s, 2H), 3.76 (t, J = 5.8 Hz, 2H); MS (ESI) (m/z) 275.1/277.1 (M+H)⁺.

References:

WO2017/205451,2017,A1 Location in patent:Paragraph 0276; 0277