Nitrogen → 3-(3,5-difluorophenyl)dihydro-2H-pyran-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of (1R,2R)-2-aminocyclohexanol hydrochloride (0.418 g, 2.76 mmol), nickel(II) chloride hexahydrate (0.328 g, 1.378 mmol) and 3,5-difluorophenylboronic acid (6.53 g, 41.3 mmol) was added NaHMDS in THF (55.1 mL, 55.1 mmol) at 10° C. dropwise under N2. After addition, the mixture was stirred at 10° C. for 20 min. 2-Propanol (113 mL) (previously bubbled by N2) was added at 0° C. and then the mixture was stirred at RT for 10 min. 3-iodo-4,4-dimethoxytetrahydro-2H-pyran (Preparation X1) (7.5 g, 27.6 mmol). in THF was added dropwise and the mixture was heated at 60° C. overnight. The reaction mixture was cooled in ice bath, added 1.0HCl until acidic and stirred for 10 min. Concentrated in vacuum. Extracted with EtOAc and the organic layer was washed with brine and concentrated. The residue was purified by column chromatography on silica gel to give 3-(3,5-difluorophenyl)dihydro-2H-pyran-4(3H)-one (1.6 g, 7.54 mmol, 27.4% yield). 1H NMR (500 MHz, CDCl3) δ ppm 6.78 (dd, J=8.24, 2.14 Hz, 2 H) 6.62-6.75 (m, 1 H) 4.21 (dd, J=11.44, 5.65 Hz, 2 H) 3.85-4.01 (m, 2 H) 3.76 (dd, J=8.55, 6.10 Hz, 1 H) 2.60-2.75 (m, 1 H) 2.48-2.60 (m, 1 H)

Provenance & Evidence