Diisobutylaluminum hydride → (R)-2-Chloro-6-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-propionic acid ethyl ester (175 mg, 0.50 mmol) in THF (5 mL) at −78° C. was added DIBAL-H (2.0 mL, 2.0 mmol, 1M solution in THF) and the resulting mixture warmed to 0° C. over 30 minutes. The reaction mixture was quenched with Rochelle's salt (1M aqueous solution) and the aqueous extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was taken up into THF (10 mL), to the resultant solution was added sodium hydride (60 mg, 1.50 mmol, 60% dispersion in mineral oil) and the resulting mixture stirred at RT for 18 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic extracts were dried (Na2SO4) and concentrated in vacuo affording (R)-2-Chloro-6-methyl-4-morpholin-4-yl-6,7-dihydro-[1,4]dioxino[2,3-d]pyrimidine as a white solid (157 mg, quantitative). LCMS: RT=2.89 min, [M+H]+=272/274.

Provenance & Evidence