Methanol → HCID 57804278, compound

Participants

Reaction Conditions

Reaction Steps

To a vial containing 4-Chloro-5-methyl-3-trifluoromethyl-1H-pyrazole (2.83 g, 15.3 mmol) was added MeOH (5 mL) and ethyl propiolate (1.94 g, 19.7 mmol) and acetic acid (100 μL). The vial was capped and the reaction mixture was heated to 80° C. for 20 h. After cooling to room temperature, the volatiles were removed in vacuo to afford the crude products, which were purified by flash chromatography on silica gel (120 g) using gradient elution (0%-75% EtOAc in hexanes over 15 column volumes). The fractions containing the E and Z esters were collected separately and concentrated in vacuo. Each product was then transferred to a separate vial using THF (10 mL). Both vials were treated with a 1.0 N solution of LiOH (10 mL). The vials were heated to 40° C. After 2 h, the solutions were cooled, and each was diluted with water (50 mL). The pH was adjusted to 1 with 4 N HCl. Each aqueous phase was extracted with EtOAc (2×25 mL). The organic phases were dried over MgSO4 and concentrated in vacuo to afford (E)-3-(4-Chloro-5-methyl-3-trifluoromethylpyrazol-1-yl)-acrylic acid (2.21 g, 57% yield) HPLC retention time=2.18 minutes. MS (ES) [M−H]− expected 253.0, found 252.9; and (Z)-3-(4-Chloro-5-methyl-3-trifluoromethylpyrazol-1-yl)acrylic acid (749 mg, 19% yield). MS (ES) [M−H]− expected 253.0, found 252.9.

Provenance & Evidence