Ammonium Chloride → 5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-2-amine

Participants

Reaction Conditions

Reaction Steps

In a 75 mL sealed tube, (S)-2-chloro-5-(1-methylpyrrolidin-2-yl)pyridine (622 mg, 3.16 mmol) and 2-(dicyclohexylphosphino)biphenyl (222 mg, 633 μmol) were combined with THF (15 ml) to give a light yellow solution. The solution was degassed with argon. Tris(dibenzylideneacetone)dipalladium (0) (290 mg, 316 μmol) was added. LiHMDS (9.49 ml of 1M solution in THF, 9.49 mmol) was added. The reaction was placed under an argon atmosphere and sealed. The reaction mixture was heated to 90° C. and stirred for 15 h. Reaction was complete by tlc. The reaction mixture was cooled to room temperature and diluted with EtOAc. The reaction mixture was poured into 150 mL sat NH4Cl and extracted with EtOAc (4×75 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography with stepwise gradient (silica gel, 40 g, 10% to 50% (60:10:1 CH2Cl2:methanol:NH4OH)/CH2Cl2) gradient to afford the desired product (560 mg, 99%). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.57-2.03 (m, 3H) 2.04-2.39 (m and overlapping s, 5H) 2.92 (t, J=8.12 Hz, 1H) 3.14-3.29 (m, 1H) 4.40 (br. s., 2H) 6.51 (d, J=8.69 Hz, 1H) 7.47 (dd, J=8.31, 2.27 Hz, 1H) 7.95 (d, J=2.27 Hz, 1H)

Provenance & Evidence