Pyrrolidine → 6-bromo-2-(tetrahydro-2H-pyran-3-yl)chroman-4-one

Participants

Reaction Steps

To a solution of 1-(5-bromo-2-hydroxyphenyl)ethanone (6.069 g, 28.23 mmol) and tetrahydro-2H-pyran-3-carbaldehyde (3.218 g, 28.23 mmol) in MeOH (50 mL) was added pyrrolidine (1.5 mL). The resulting solution was heated to reflux and monitored with LC-MS. 50% conversion was achieved after 2 h. After 12 h, there was no improvement in conversion. The reaction mixture was cooled down to room temperature and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel and eluted with EA in hexane (0-30%) to produce 1.981 g of 6-bromo-2-(tetrahydro-2H-pyran-3-yl)chroman-4-one. 1.321 g of 6-bromo-2-(tetrahydro-2H-pyran-3-yl)chroman-4-one was further purified by preparative HPLC to give (S/R)-6-bromo-2-((S/R)-tetrahydro-2H-pyran-3-yl)chroman-4-one (A) (669 mg, polar isomer on preparative HPLC) and (S/R)-6-bromo-2-((R/S)-tetrahydro-2H-pyran-3-yl)chroman-4-one (B)(512 mg, less polar isomer on preparative HPLC). MS ESI+ve m/z 311 (M+H)+.

Provenance & Evidence