Methyl chlorodifluoroacetate → HCID 86650630, compound

Participants

Reaction Conditions

Reaction Steps

t-butyl-6-chloro-5-iodopyrazin-2-yl((tetrahydro-2H-pyran-4-yl)methyl)carbamate (0.0569 g, 0.125 mmol), methyl 2-chloro-2,2-difluoroacetate (0.047 ml, 0.063 g, 0.439 mmol), potassium fluoride (0.015 g, 0.251 mmol), and copper (I) iodide (0.100 g, 0.527 mmol) were dissovled in anhydrous DMF (0.80 ml) and placed under argon. The reaction mixture was then heated at 115° C. for 17 hr. It was allowed to cool to ambient temperature. The reaction mixture was filtered through a pad of Celite. The filtrate was poured into brine (25 ml). This was extracted with EtOAc (3×25 ml). The combined extracts were washed with H2O (1×25 ml) followed by brine (1×25 ml). The organic layer was dried (Na2SO4), filtered, and the solvent removed in vacuo to give 0.0401 g of crude product. The resulting residue was subjected to silica gel column chromatography. Elution using 25 EtOAc/75 heptane to 100 EtOAc gave 0.0569 g (55%) of 6-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)-5-(trifluoromethyl)pyrazin-2-amine. LCMS (m/z): 296.0 (MH+), retention time=0.93 min. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.39 (qd, J=12.33, 4.50 Hz, 2 H) 1.68 (d, J=11.35 Hz, 3 H) 1.80-2.00 (m, J=14.87, 7.63, 7.63, 3.52 Hz, 1 H) 3.32-3.47 (m, 4 H) 4.01 (dd, J=11.35, 3.52 Hz, 2 H) 5.26 (br. s., 1 H) 7.76 (s, 1 H).

Provenance & Evidence