Diethyl azodicarboxylate → Tert-butyl 2-[(2-bromo-5-methoxyphenoxy)methyl]-2,5-dihydro-1H-pyrrole-1-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl 2-(hydroxymethyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (8.96 g, 0.45 mol, from Specialty Chemicals, Inc.) and 2-bromo-5-methoxyphenol (9.32 g, 0.46 mol) in THF (180 mL) was added DEAD (20.5 mL) in toluene (40 wt %) dropwise at 0° C. The reaction was stirred for 21 h at RT and the solvent was evaporated. The residue was suspended in methyl tert-butylether (50 mL) and the solution was filtered and concentrated. The resulting residue was dissolved in DCM, washed with 0.6N NaOH (2×25 mL) and the layers were separated. The organic layer was dried with Na2SO4 and the solvent was evaporated. The crude product was purified using an ISCO instrument (330 g RediSep® column), eluting with a gradient of ethyl acetate in heptane (from 0%-20% ethyl acetate over 6 minutes, then 29% ethyl acetate for 20 min) to afford 16.4 g of the title product.

Provenance & Evidence