Methyl chloroformate → methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of N-[(3R,4S)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine (4.50 g, 17 mmole) in CH2Cl2 (0.1 M, 170 mL) under N2 at 0° C. was added triethyl amine (7.09 mL, 3.0 eq.). Methyl chloroformate (1.44 mL, 1.1 eq.) was added drop-wise over 15 min. After 1 hour, the reaction mixture was poured into saturated aqueous NaHCO3 (150 mL). The aqueous layer was extracted with CH2Cl2 (1×200 ml), dried with MgSO4, filtered and concentrated. Purification with Biotage MPLC (40 g, 10-50% ethyl acetate in heptane gradient) provided 5.35g (98%) of methyl (3R,4S)-3-[(3,6-diethylpyrazin-2-yl)amino]-4-ethoxypyrrolidine-1-carboxylate as an oil. IR (liq.) 2972, 2937, 2877, 2338, 1937, 1708, 1581, 1546, 1499, 1453, 1392, 1189, 1174, 1135, 1103 (s) cm−1 HRMS (ESI) calcd for C16H26N4O3+H1 323.2083. found 323.2089. Anal. Calcd for C16 H26 N4O3: C, 59.61; H, 8.13; N, 17.38. Found: C, 59.23; H, 8.35; N, 17.33.

Provenance & Evidence