Nitrogen → Ethyl 5-chloromethylisoxazole-3-carboxylate

Participants

Reaction Steps

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 5-hydroxymethyl-isoxazole-3-carboxylic acid ethyl ester (3.00 g, 17.53 mmol) in dry CH2Cl2 (30.0 mL) was treated at 0° C. with Et3N (3.17 mL, 22.79 mmol) followed by DMAP (214 mg, 1.75 mmol) and Ms-Cl (2.04 mL, 26.29 mmol). The reaction mixture was stirred at rt for 4 h before being quenched with water (50 mL), extracted with CH2Cl2 (50 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give crude 5-chloromethyl-isoxazole-3-carboxylic acid ethyl ester as an orange oil. A solution of 1.01 g of this crude material in acetone (8.0 mL) was treated, under inert atmosphere (N2) with K2CO3 (1.260 g, 9.12 mmol) followed by 4-nitro-1H-pyrazole (343 mg, 3.04 mmol) and TBA bromide (195 mg, 0.61 mmol). The resulting mixture was stirred at rt overnight. Water (50 mL) and EA (50 mL) were added. The aq. layer was extracted with EA (50 mL) and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (50:50 hept-EA) gave the title compound as a yellow oil. TLC: rf (50:50 hept-EA)=0.31. LC-MS-conditions 02: tR=0.86 min.

Provenance & Evidence