Triisopropyl borate → HCID 44254049, compound

Participants

Reaction Conditions

Reaction Steps

To a 1 L 3-neck flask equipped with mechanical stirrer, thermometer, and addition funnel under an atmosphere of nitrogen was charged a solution of (R)-1-(4-bromophenethyl)-2-methylpyrrolidine (26.8 g, 100 mmol) in anhydrous THF (250 mL). The reaction mixture was then cooled to an internal temperature of −78° C. A solution of n-butyl lithium (2.5M in hexane, 52 mL, 130 mmol) was added dropwise, maintaining an internal temperature below −70° C. Once addition was complete, stirring was continued an additional 15 min prior to the addition of triisopropyl borate (75 g, 400 mmol), followed by a rinse with 50 mL anhydrous THF, maintaining an internal temperature below −65° C. during addition. The reaction mixture was then allowed to warm to ambient temperature over 1.5 h, and was then quenched by dropwise addition of 2 N HCl (100 mL). The resulting mixture was stirred overnight, and the solvent volume was reduced to about 150 mL. The resulting suspension was cooled in an ice bath and filtered, rinsing sparingly with cold isopropanol. The filtrate volume was again reduced to 50 mL and the process was repeated. The filter cakes were combined, taken up in boiling isopropanol (250 mL), dissolving most, but not all of the solids. The mixture was then cooled in an ice bath and filtered, then the filtrate was concentrated to half volume and the process was repeated to provide two additional crops. A white solid was obtained as the title compound (23 g). LCMS m/z=234.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.41 (d, J=6.6 Hz, 3H), 1.59-1.68 (m, 1H), 1.89-2.00 (m, 2H), 2.15-2.22 (m, 1H), 3.00-3.07 (m, 2H), 3.11-3.19 (m, 2H), 3.37-3.50 (m, 2H), 3.57-3.65 (m, 1H), 4.80-6.75 (bs, 3H), 7.27 (d, J=7.6 Hz, 2H), 7.76 (d, J=8.2 Hz, 2H).

Provenance & Evidence