Tetrahydro-2-(2-propynyloxy)-2H-pyran → HCID 21904872, compound

Participants

Reaction Conditions

Reaction Steps

A suspension of (RS)-trifluoro-methanesulfonic acid 2-[(4-cyano-benzylcarbamoyl)-methoxy-methyl]-3-fluoro-phenyl ester (520 mg, example 279.1) in DMF (10 ml) was heated to 100° C. and treated with TEA (0.49 ml), tetrahydro-2-(2-propynyloxy)-2H-pyrane (0.33 ml) and Cu(I)I (18 mg). The reaction mixture was degassed by passing a stream of Argon through the reaction mixture. Then bis(triphenylphosphine)palladium(II)chloride (32 mg) was added. The reaction was heated for 6 hrs at 100° C. After cooling to rt, the mixture was concentrated. The residue was taken up in EtOAc and H2O. After filtration through a glass microfibre filter, phases were separated. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by flash chromatography (cyclohexane=>cyclohexane/EtOAc 3:2) to give (RS)-N-(4-cyano-benzyl)-2-{2-fluoro-6-[3-(tetrahydro-pyran-2-yloxy)-prop-1-ynyl]-phenyl}-2-methoxy-acetamide as off-white solid. MS 454.3 ([M+NH4]+)

Provenance & Evidence