Sodium Hydroxide → Methyl 2-chloro-6-cyclopropylpyrimidine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a 5 mL glass microwave tube methyl 2,4-dichloropyrimidine-6-carboxylate (621 mg, 3.00 mmol) (Astatech Inc.) and Amphos (53.1 mg, 0.075 mmol) were treated with cyclopropylzinc(II) bromide (Rieke, 0.5 M in THF) (1.2 mL, 6.00 mmol) via syringe under an atmosphere of argon. The solution was then heated in the microwave at 80° C. for 20 min. The mixture was treated with EtOAc and 1N NaOH resulting in a white suspension as the zinc hydroxide salts precipitated out. The suspension was extracted with EtOAc (50 mL) a second time and washed with brine and dried over Na2SO4, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 100% DCM) to give methyl 2-chloro-6-cyclopropylpyrimidine-4-carboxylate (254 mg, 40%) as a clear, colorless, viscous oil. MS (ESI, pos. ion) m/z: 213.1 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (1H, s), 3.99-4.04 (3H, m), 2.06-2.15 (1H, m), 1.20-1.31 (4H, m).

Provenance & Evidence