Sodium Bicarbonate → benzyl (3R,4S)-3-({3,6-diethyl-5-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]pyrazin-2-yl}amino)-4-ethoxypyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of 3-iodo-6-methoxy-2-(trifluoromethyl)pyridine (162 mg, 3 eq.) and Zinc chloride (0.5 M THF, 9 eq.) in THF (2.67 ml) under N2 at −78° C. was added t-butyl lithium (9 eq.). After 5 min, the reaction mixture was warmed to ambient temperature and cannula'd into a flask containing benzyl (3R,4S)-3-[(3,6-diethyl-5-iodopyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate (120 mg) and palladium tetrakis (31 mg). The reaction mixture was heated at reflux for 16 h, poured into saturated sodium bicarbonate (50 ml), extracted 3×50 ml of CH2Cl2, dried MgSO4, filtered and concentrated. Purification via MPLC chromatography eluting with 20–45% ethyl acetate/heptane afforded the title compound as an amorphous solid (63 mg, 53%):

Provenance & Evidence