Sodium hydride → tert-Butyl 4-((2-chloropyrimidin-4-yl)oxy)piperidine-1-carboxylate

Temperature

0 °C

To a solution of tert-butyl 4-hydroxypiperidine-1-carboxylate (1.0 g, 5.0 mmol, Aldrich) in DMF (15.0 mL) at 0° C. was added sodium hydride (0.55 g, 15.0 mmol, 65% dispersion in mineral oil, commercially available from Sigma-Aldrich Corporation). in several portions. After stirring at 0° C. for 10 min, 2,4-dichloropyrimidine (745 mg, 5.0 mmol, commercially available from Sigma-Aldrich Corporation) in DMF (10.0 mL) was added. The resulting mixture was stirred at 0° C. for 10 min and at room temperature for 2 h and then quenched with saturated NH4Cl aqueous solution (1.5 mL). The reaction mixture was diluted with EtOAc and H2O and the aqueous solution was extracted further with EtOAc (2×). The combined organic extracts were washed with H2O (3×) and brine, dried (Na2SO4) and evaporated. The residual was purified by flash chromatography (0 to 50% EtOAc/hexanes) to yield 409.3 mg (26%) of the product as an off-white semi-solid. MS (ESI) 314 (M+H).

1. stirringThe resulting mixture was stirred at 0° C. for 10 min and at room temperature for 2 h
2. customquenched with saturated NH4Cl aqueous solution (1.5 mL)
3. additionThe reaction mixture was diluted with EtOAc and H2O
4. extractionthe aqueous solution was extracted further with EtOAc (2×)
5. washThe combined organic extracts were washed with H2O (3×) and brine
6. dry with materialdried (Na2SO4)
7. customevaporated
8. customThe residual was purified by flash chromatography (0 to 50% EtOAc/hexanes)

ORD record

ord-5d116eb0c38d4fd886386957f81e60d1

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513424B2