Phosphoric Acid → (3-[4-(Tert-butoxycarbonyl)piperazin-1-YL]phenyl)boronic acid

Temperatur

-70 °C

Into a 250-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl 4-(3-bromophenyl)piperazine-1-carboxylate (3.8 g, 11.14 mmol, 1.00 equiv) in toluene/tetrahydrofuran=1:1 (40 mL). This was followed by the addition of n-BuLi (4.9 mL, 2.5M/L) dropwise with stirring at −70° C. The resulting solution was stirred for 30 min at −70° C. To this was added triisopropyl borate (2.5 g, 13.30 mmol, 1.19 equiv) dropwise with stirring at −70° C. The mixture was warmed to 0° C., the reaction was then quenched by the addition of 13 mL of saturated ammonium chloride and 3.4 mL of water. Phosphoric acid (85 wt %, 1.5 g, 1.2 equiv) was added and the mixture was stirred for 30 min. The organic layer was separated and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was dissolved in 20 mL of toluene. The product was precipitated by the addition of 80 mL of heptane. The solids were washed with 20 mL of heptane and collected by filtration. This resulted in 2.9 g (85%) of 3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid as a white solid.

1. customInto a 250-mL 3-necked round-bottom flask purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. stirringThe resulting solution was stirred for 30 min at −70° C
4. stirringwith stirring at −70° C
5. temperatureThe mixture was warmed to 0° C.
6. customthe reaction was then quenched by the addition of 13 mL of saturated ammonium chloride and 3.4 mL of water
7. stirringthe mixture was stirred for 30 min
8. customThe organic layer was separated
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated under vacuum
11. dissolutionThe residue was dissolved in 20 mL of toluene
12. customThe product was precipitated by the addition of 80 mL of heptane
13. washThe solids were washed with 20 mL of heptane
14. filtrationcollected by filtration
15. customThis resulted in 2.9 g (85%) of 3-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenylboronic acid as a white solid

ORD-Eintrag

ord-6a7cc92749544b01b4b73898764da48e

Quelldatensatz

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08541448B2