Tetrahydro-4H-pyran-4-one → HCID 86651586, compound

Participants

Reaction Conditions

Reaction Steps

In a 100 mL round bottomed flask containing 2,4-dichloropyrimidin-5-amine (1.0 g, 6.10 mmol) in 16.5 mL of dichloromethane was added dihydro-2H-pyran-4 (3H)-one (0.794 g, 7.93 mmol), cooled to 0° C. then added the solution of titanium tetrachloride (0.740 ml, 6.71 mmol) in 10 mL of dichloromethane. The reaction was removed from the ice bath and with continued stirring, slowly warmed to room temperature. After 3.5 h, sodium cyanoborohydride (1.15 g, 18.29 mmol) was added in 4 equal portions over 10 minutes and the reaction was stirred at room temperature for 16 h. The suspension was diluted with water (150 mL) and transferred to an appropriate separatory funnel. The layers were separated and then extracted the aqueous layer with MTBE (1×150 mL). The organic layers were combined, washed with sat. NaCl, dried over Na2SO4, filtered and concentrated in vacuo affording a clear orange oil. The crude oil was purified by silica chromatography (30% EtOAc/Hexanes); the appropriate fractions were combined and concentrated in vacuo to afford 2,4-dichloro-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-5-amine (0.336 g, 60% pure, 22% yield). MS [M+H] found 249.1.

Provenance & Evidence