Morpholine → HCID 66600229, compound

Participants

Reaction Steps

A solution of 5-(bromomethyl)-2-fluoropyridine (26.000 g, 137 mmol) in THF (30 mL) was cooled to −30° C. and morpholine (17.88 mL, 205 mmol) was slowly added. After 5 min, triethylamine (57.2 mL, 410 mmol) was slowly added. Following addition, the cooling bath was removed and the mixture was allowed to warm to ambient temperature. After 30 min, the mixture was filtered through a fine-fritted funnel and the filtrate was concentrated to give an orange oil. The crude material was purified by chromatography through a Thompson Instruments pre-packed silica gel (330 gram) column eluting with a gradient of 0% to 100% EtOAc in hexane over 50 min to give 4-((6-fluoropyridin-3-yl)methyl)morpholine (15.767 g, 80 mmol, 58.7% yield) as an orange oil. 1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H); 7.79 (td, J=8.07, 2.45 Hz, 1H); 6.90 (dd, J=8.31, 2.84 Hz, 1H); 3.67-3.72 (m, 4H); 3.49 (s, 2H); 2.39-2.48 (m, 4H). m/z (ESI, +ve ion) 197.1 (M+H)+.

Provenance & Evidence