2-(4-(trifluoroMethyl)phenyl)cyclopropanecarboxylic acid synthesis

Yield:2262-03-5 93%

Reaction Conditions:

with water;sodium hydroxide in ethanol at 20; for 1.5 h;

Steps:

6.3 Step 3: 2-(4-(trifluoromethyl)phenyl)cyclopropanecarboxylic acid

In a 50 mL round-bottomed flask was added ethyl 2-(4-(trifluoromethyl)phenyl) cyclopropanecarboxylate (0.700 g, 2.71 mmol) in ethanol (7 ml) to give a colorless solution. NaOH 1M in water (7.00 ml, 7.00 mmol) was added. The resulting mixture was stirred at 20°C for 1.5 hour. Concentrated to ca. 5 mL on rotovap. Acidified to pH 3 with HCI 2M in water (2.60 ml, 5.20 mmol). Extracted the aqueous layer with EtOAc (2 x 15 mL). The combined organic layers were washed with Brine (15 mL). The organic layer was dried over MgS0₄, filtered and concentrated to give 2-(4- (trifluoromethyl)phenyl) cyclopropanecarboxylic acid (582 mg, 2.53 mmol, 93% yield). ¹H NMR (400 MHz, DMSO-dg) δ ppm 12.42 (br. s., 1 H), 7.58 - 7.65 (m, J = 8.2 Hz, 2H), 7.36 - 7.44 (m, J = 8.2 Hz, 2H), 2.52 - 2.54 (m, 1 H), 1.87 - 1.96 (m, 1 H), 1.49 (dt, J = 9.2, 4.8 Hz, 1 H), 1.41 (ddd, J = 8.4, 6.3, 4.5 Hz, 1 H).

References:

WO2019/84662,2019,A1 Location in patent:Page/Page column 145-146