Methyl iodide → 1-(5-Bromopyrimidin-2-yl)-4-methoxy-piperidine-4-carboxylic acid

Temperature

0 °C

A solution of methyl 1-(5-bromopyrimidin-2-yl)-4-hydroxypiperidine-4-carboxylate (0.2 g, 0.63 mmol) in DMF (25 mL) was cooled to 0° C. followed by portion wise addition of NaH (60% dispersion in mineral oil, 0.05 g, 1.08 mmol) and the mixture stirred at 0° C. for 45 min followed by addition of MeI (0.20 mL, 3.16 mmol). The temperature of the reaction was slowly raised to rt and left to stir for 4 h. The reaction was then cooled to 0° C. and quenched by drop wise addition of saturated NH4Cl solution (50 mL), extracted with EtOAc (3×100 mL) and the combined organics washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude residue was purified over 100-200 M silica-gel using 3% EtOAc:hexane to obtain the product as an off-white solid (0.12 g, 57% yield). MS: 330.18 [M+H]+.

1. temperatureThe temperature of the reaction was slowly raised to rt
2. waitleft
3. stirringto stir for 4 h
4. temperatureThe reaction was then cooled to 0° C.
5. customquenched by drop wise addition of saturated NH4Cl solution (50 mL)
6. extractionextracted with EtOAc (3×100 mL)
7. washthe combined organics washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe crude residue was purified over 100-200 M silica-gel

ORD record

ord-8cdb0cce18dd476fb8507171a24c8b98

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181234B2