Hydrochloric Acid → (R)-Benzyl 2-((5-bromo-1H-indol-3-yl)methyl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

3-(N-Benzyloxycarbonyl-2(R)-pyrrolidinylcarbonyl)-5-bromo-1H-indole (WO-A-92/06973; 0.67 g, 1.57 mmol) was dissolved in dry tetrahydrofuran (20 ml) and, at room temperature under nitrogen, lithium borohydride (2M solution in tetrahydrofuran; 1.2 ml, 2.4 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours, heated under reflux for 16 hours, then allowed to cool to room temperature. 2M Hydrochloric acid (10 ml) was added dropwise and the reaction mixture then partitioned between ethyl acetate and water. The separated organic phase was washed with saturated aqueous sodium bicarbonate solution (×2) and brine (×1), dried (Na2SO4), and evaporated under reduced pressure to give a colourless oil. Purification by column chromatography on silica gel, eluting with dichloromethane, gave the title compound as an oil (0.32 g). Rf 0.20 (SS 16). Found: C,59.94; H,5.07; N,6.58. C21H21BrN2O2 ; 0.10 CH2Cl2 requires C,60.08; H,5.07; N,6.64%. δ(CDCl3)--mixture of rotamers: 1.63-1.90 (4H, m), 2.60-2.82 (1H, m), 3.10-3.28 (1H, m), 3.30-3.54 (2H, m), 4.18 (1H, m), 5.15-5.25 (2H, m), 5.30 (0.2H, s, CH2Cl2), 6.90 and 6.95 (1H, 2×s), 7.05-7.50 (7H, m), 7.70 and 7.85 (1H, 2×s), 8.25 (1H, br s).

Provenance & Evidence