Formaldehyde → HCID 57986840, compound

Temperature

-78 °C

To a cooled (−78° C.) and stirred solution of 4-fluoro-4-thiazol-2-yl-piperidine-1-carboxylic acid tert-butyl ester (3.65 g, 12.7 mmol) in THF (20 mL) was added n-BuLi (1.33 mL, 1.05 eq., 10.0 M in hexanes). The mixture was stirred at this temperature for 30 minutes. Then a suspension of paraformaldehyde (383 mg, 1 eq.) in THF (10 mL) was added in. The resulting mixture was continued to stir at −78° C. for another 30 minutes and gradually warmed to room temperature overnight. The reaction was quenched by addition of water (10 mL). The mixture was extracted with EtOAc. The organic phase was washed with brine and dried over Na2SO4. After removal of the solvent, the crude product was purified on silica gel (60% EtOAc in hexanes) to afford the desired product as a pale yellow solid.

1. additionwas added in
2. stirringto stir at −78° C. for another 30 minutes
3. temperaturegradually warmed to room temperature overnight
4. customThe reaction was quenched by addition of water (10 mL)
5. extractionThe mixture was extracted with EtOAc
6. washThe organic phase was washed with brine
7. dry with materialdried over Na2SO4
8. customAfter removal of the solvent
9. customthe crude product was purified on silica gel (60% EtOAc in hexanes)

ORD record

ord-39609e8c7e8644e092d25d1c1dc99120

Source dataset

uspto-grants-2009_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07638541B2