Benzeneethanamine, alpha-methyl-, phosphate (1:1) → Methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 20 mL glass microwave tube was charged with methyl 2,4-dichloropyrimidine-5-carboxylate (Aldrich, St. Louis, Mo., 831 mg, 4.01 mmol and Amphos (Aldrich, St. Louis, Mo., 71.1 mg, 0.100 mmol) were treated with cyclopropylzinc(II) bromide (Rieke Metals, Lincoln, Nebr., 0.5 M in THF, 16.1 mL, 8.03 mmol) via syringe under an atmosphere of argon. The solution was then heated in the microwave at 80° C. for 20 min. The reaction mixture was treated with EtOAc and then with 1 N NaOH resulting in a white suspension as the zinc hydroxide salts precipitated. It was extracted with EtOAc (50 mL) a second time and washed with brine and dried over anhydrous Na2SO4, filtered and concentrated. Purification of the crude residue on the ISCO Combiflash Rf (40 g Redisep column, using 100% DCM) afforded two readily separable peaks. The first eluting peak was found to be methyl 2-chloro-4-cyclopropylpyrimidine-5-carboxylate (269 mg, 1.26 mmol, 31.5% yield) as a white amorphous solid upon concentration. MS (ESI, pos. ion) m/z: 213.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 8.91 (1H, s), 3.97 (3H, s), 3.12-3.20 (1H, m), 1.34-1.40 (2H, m), 1.20-1.27 (2H, m).

Provenance & Evidence