Tetrahydrofuran → Tert-Butyl 4-(2-(hydroxymethyl)phenyl)piperidine-1-carboxylate

4-(2-Carboxyphenyl)piperidine-1-carboxylic acid t-butyl ester (5.0 g, 16 mmol, 1.0 eq.) and THF (130 mL, 1.7 mol) were combined at room temperature under nitrogen. Boranc dimethyl sulfide complex (2.9 mL, 33 mmol, 2.0 eq.) was added dropwise and the mixture was stirred for 5 minutes, then heated at reflux for 1 hour. The mixture was cooled to room temperature, and the reaction was quenched dropwise with MeOH (40 mL), then concentrated by rotary evaporation. The material was azeotroped with MeOH (2×40 mL). The mixture was then diluted with EtOAc (100 mL), and washed with 1 M HCl (2×50 mL), then NaHCO3 (2×50 mL), then saturated aqueous NaCl (1×50 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to yield 4-(2-hydroxymethylphenyl)piperidine-1-carboxylic acid t-butyl ester (4.8 g) as a clear, light yellow oil that solidified upon sitting.

1. customwere combined at room temperature under nitrogen
2. additionBoranc dimethyl sulfide complex (2.9 mL, 33 mmol, 2.0 eq.) was added dropwise
3. temperatureheated
4. temperatureat reflux for 1 hour
5. customthe reaction was quenched dropwise with MeOH (40 mL)
6. concentrationconcentrated by rotary evaporation
7. customThe material was azeotroped with MeOH (2×40 mL)
8. additionThe mixture was then diluted with EtOAc (100 mL)
9. washwashed with 1 M HCl (2×50 mL)
10. dry with materialThe organic layer was dried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo

ORD record

ord-127561c35e09445dabc5f2cfc17858eb

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08604058B2