Carbon tetrabromide → tert-Butyl (2R)-2-(bromomethyl)pyrrolidine-1-carboxylate

Participants

Reaction Steps

To a solution of (R)-pyrrolidin-2-ylmethanol (0.7 g, 6.93 mmol) in CH2Cl2 (5 mL) was added (Boc)2O (1.66 g, 7.62 mmol) and triethylamine (1.40 g, 13.86 mmol) at 0° C. After stirring at 0° C. for about 10 minutes, the reaction mixture was allowed to stir at room temperature for 16 h. The mixture was quenched with aqueous acetic acid, then diluted with CH2Cl2 (20 mL), extracted with H2O (2×20 mL). The organics were dried over Na2SO4, filtered and concentrated to give (R)-tert-butyl (hydroxymethyl)pyrrolidine-1-carboxylate (1.26 g, 91%) as a solid. A solution of (R)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (1.26 g, 6.26 mmol) in CH2Cl2 (25 mL) was treated with CBr4 (3.13 g, 9.45 mmol) and PPh3 (2.48 g, 9.45 mmol) at 0° C. under N2 atmosphere. The reaction mixture was allowed to stir at room temperature for 16 h. Silica gel was added to the mixture, and then the mixture was concentrated to dryness. Purification by flash column chromatography (silica gel, Hexane/EtOAc, 100:0 to 3:1) gave the title compound (0.99 g, 60%) as a solid: 1H NMR (500 MHz, DMSO-d6) δ 4.08-3.98 (m, 1H), 3.69-3.50 (m, 1H), 3.48-3.21 (m, 3H), 2.10-1.75 (m, 4H), 1.47 (s, 9H); ESI MS m/z 164 [M+H]+.

Provenance & Evidence