18-Crown-6 → HCID 58293640, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 2-(bis(2,2,2-trifluoroethoxy)phosphoryl)acetate (2.460 mL, 11.63 mmol) in 70 mL of THF at −78° C. was added 18-CROWN-6 (9.14 g, 34.6 mmol). Added KHMDS (23.05 mL, 11.53 mmol) dropwise over 15 min and allowed the resulting mixture to stir at −78° C. for 30 min. Then 4,6-dichloropyrimidine-5-carbaldehyde (1.7 g, 9.61 mmol) was added in 20 mL of THF and the resulting mixture was allowed to stir at −78° C. for 1.5 h. The reaction was quenched with about 25 mL sat'd NH4Cl, allowed to warm to RT and then most of the THF was removed by rotary evaporator. The resulting mixture was diluted with 1:1 hexane/ethyl acetate, washed with 1N HCl, sat'd aq sodium bicarbonate and brine, dried (MgSO4), filtered through a pad of silica gel and concentrated in vacuo to afford an oil (2.8 g). The residue was purified by silica gel chromatography (80 g ISCO cartridge, 0-80% ethyl acetate/hexane) to afford Example 116A (1.55 g, 69%) as an oil, which was contaminated with ˜10% of the (E)-olefin isomer. The material was used without further purification. LRMS (ESI): 233.1 [M+H]+.

Provenance & Evidence