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

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).

1. customat ambient temperature
2. customthe pot temperature below 25° C
3. temperatureCool the solution to 0-5° C.
4. stirringStir at 0-5° C. for 10-15 minutes
5. customremove
6. temperaturecooling bath
7. temperaturemaintaining a pot temperature of 30-35° C
8. stirringStir the resulting mixture for 1 hour
9. customLayer separate
10. extractionre-extract the aqueous layer with MTBE (655 mL)
11. washCombine organics and wash with water (2×655 mL) and brine (2×655 mL)
12. dry with materialDry the MTBE solution over sodium sulfate
13. filtrationfilter
14. concentrationconcentrate in vacuo
15. customto afford 169.1 g of crude oil (theory=139.1 g)
16. stirringstir 5 minutes
17. customLayer separate
18. extractionre-extract the aqueous layer with MTBE (655 mL)
19. stirringStir 5 minutes
20. customseparate
21. washCombine the MTBE extracts and wash with water (655 mL)
22. dry with materialdry over sodium sulfate
23. filtrationfilter
24. concentrationconcentrate in vacuo

ORDレコード

ord-ccbf88967ae942c5ae3a3f290cf2795d

出典データセット

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07384934B2