Hydrochloric Acid → (S)-2-(1,4-Dibenzylpiperazin-2-yl)ethanol

Participants

Reaction Steps

Combine (S)-1,4-dibenzyl-2-vinyl-piperazine (131.0 g, 0.448 mol) and THF (500 mL) at ambient temperature. Add a 0.5M THF solution of 9-borabicyclo[3.3.1] nonane (9-BBN) (985.5 mL, 0.493 mol) over 20 minutes, keeping the pot temperature below 25° C. Stir the resulting mixture at ambient temperature for 16-18 hours. Cool the solution to 0-5° C. and quench with 3N NaOH (164.3 mL, 0.493 mol) over 5-10 minutes. Stir at 0-5° C. for 10-15 minutes and remove cooling bath. Add a 30% aqueous solution of hydrogen peroxide (160.2 mL, 1.57 mol) over 1 hour, maintaining a pot temperature of 30-35° C. Stir the resulting mixture for 1 hour and dilute with water (1.31 L) and MTBE (1.31 L). Layer separate and re-extract the aqueous layer with MTBE (655 mL). Combine organics and wash with water (2×655 mL) and brine (2×655 mL). Dry the MTBE solution over sodium sulfate, filter and concentrate in vacuo to afford 169.1 g of crude oil (theory=139.1 g). Treat the crude with 5N HCl (358 mL, 1.79 moles) and stir 5 minutes. Add water (250 mL) and stir 15-20 minutes. Add heptane (1.31 L) and stir 5 minutes. Layer separate and re-extract the aqueous layer with MTBE (655 mL). Discard these organic extracts and add 5N NaOH (403 mL, 2.02 moles) to the aqueous portion. Stir 5 minutes then dilute with MTBE (1.31 L) and layer separate. Re-extract the aqueous layer with MTBE (655 mL). Combine the MTBE extracts and wash with water (655 mL), then dry over sodium sulfate, filter and concentrate in vacuo to afford 137.8 g (99.0%) of the title compound. 1H NMR (500 MHz, DMSO-d6) δ 1.87 (m, 1H), 2.03 (m, 1H), 2.33 (m, 2H), 2.43 (m, 1H), 2.50 (d, 1H), 2.66 (d, 1H), 2.83 (m, 1H), 2.93 (m, 1H), 3.39 (d, 1H), 3.50 (m, 1H), 3.74 (m, 1H), 3.88 (m, 1H), 4.18 (d, 1H), 4.80 (bs, 1H), 7.26 (m,2H), 7.32 (m, 8H).

Provenance & Evidence