Cesium carbonate → Ethyl 1-[2-fluoro-3-(hydroxymethyl)phenyl]piperidine-4-carboxylate

Temperature

100 °C

Under argon atmosphere, [(3-bromo-2-fluorobenzyl)oxy](tert-butyl)dimethylsilane (2 g) and ethyl piperidine-4-carboxylate (1.6 g) were mixed with toluene (30 ml), and Pd2(dba)3 (150 mg), BINAP (300 mg), and cesium carbonate (3.2 g) were added thereto, followed by stirring at 100° C. for 1 hour. The reaction mixture was cooled to room temperature, and EtOAc was added thereto, followed by filtration using Celite as a filtration adjuvant. The filtrate was concentrated under reduced pressure, the residue was then mixed with THF (30 ml), and a 1M TBAF/THF solution (12 ml) was added thereto, followed by stirring at room temperature for 1 hour. To the reaction mixture were added EtOAc and water, and the organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain ethyl 1-[2-fluoro-3-(hydroxymethyl)phenyl]piperidine-4-carboxylate (1.02 g).

1. additionwere added
2. temperatureThe reaction mixture was cooled to room temperature
3. filtrationfollowed by filtration
4. concentrationThe filtrate was concentrated under reduced pressure
5. additionthe residue was then mixed with THF (30 ml)
6. additiona 1M TBAF/THF solution (12 ml) was added
7. stirringby stirring at room temperature for 1 hour
8. additionTo the reaction mixture were added EtOAc and water
9. dry with materialthe organic layer was dried over Na2SO4
10. concentrationconcentrated under reduced pressure
11. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

ORD record

ord-d5255b076d864d4aa2a978abae59481f

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09051283B2