2-[4-(tert-Butoxycarbonyl)piperazin-1-yl]benzoic acid → tert-Butyl 4-[2-(hydroxymethyl)phenyl]piperazine-1-carboxylate

4-(2-Carboxyphenyl)piperazine-1-carboxylic acid t-butyl ester (3.5 g, 11.3 mmol, 1.0 eq.) and THF (91.3 mL) were combined at room temperature under nitrogen. Borane-dimethyl sulfide complex (2.00 mL, 22.5 mmol, 2.0 eq.) was added dropwise and the mixture was stirred for 5 minutes, then heated at the reflux temperature for 1.5 hours. The mixture was cooled to room temperature, and the reaction was quenched slowly with MeOH (20 ml), then concentrated by rotary evaporation. The material was azeotroped with MeOH (2×20 ml). The crude product was dissolved in EtOAc (50 ml), and washed with cold 1M HCl (2×25 ml), then NaHCO3 (2×25 ml). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to yield the title compound (1.3 g) as a clear oil that solidified upon sitting.

1. customwere combined at room temperature under nitrogen
2. additionBorane-dimethyl sulfide complex (2.00 mL, 22.5 mmol, 2.0 eq.) was added dropwise
3. temperatureheated at the reflux temperature for 1.5 hours
4. customthe reaction was quenched slowly with MeOH (20 ml)
5. concentrationconcentrated by rotary evaporation
6. customThe material was azeotroped with MeOH (2×20 ml)
7. dissolutionThe crude product was dissolved in EtOAc (50 ml)
8. washwashed with cold 1M HCl (2×25 ml)
9. dry with materialThe organic layer was dried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORD record

ord-419b0df1f21140f3bc24dcb38dbd80c2

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778949B2