Cesium carbonate → benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-hydroxypyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 250 ml round bottom flask was charged with benzyl (3R,4S)-3-amino-4-hydroxypyrrolidine-1-carboxylate (4.97 g, 21.04 mmol), 2-chloro-3,6-diethylpyrazine (3.95 g, 23.15 mmol), Pd2(dba)3 (10 mol %, 1.926 g), 2-dicyclohexylphosphino-2′-(N, N-dimethyl amino)biphenyl (20 mol %, 1.66 g), ethylene glycol dimethyl ether (110 mL), and Cs2CO3 (9.57 g) respectively. The reaction mixture was stirred at 80° C. for 20 hr. It was cooled, diluted with Et2O (100 ml), poured into NaHCO3 (80 ml), extracted with CH2Cl2 (150 ml×3), dried (MgSO4), and concentrated. Purification with Biotage MPLC (35% EtOAc in heptane) provided 4.6 g (60%) of benzyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-hydroxypyrrolidine-1-carboxylate as an oil. IR (liq.) 2969, 2344, 1996, 1952, 1703, 1691, 1546, 1499, 1449, 1426, 1395, 1359, 1175, 1133, 1095, cm−1. HRMS (FAB) calcd for C20H26N4O3+H1 371.2083. found 371.2089.

Provenance & Evidence