Methyl methoxyacetate → 1-[5-Chloro-4-(tetrahydro-pyran-2-yloxymethyl)-pyridin-3-yl]-2-methoxy-ethanone

Temperature

-78 °C

3-Bromo-5-chloro-4-(tetrahydro-pyran-2-yloxymethyl)-pyridine (0.30 g, 0.98 mmol) was dissolved in anhydrous THF (15 mL) under Ar and the solution was cooled to −78° C. n-BuLi (0.62 mL, 1.6 M in hexanes, 0.98 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 0.5 h. Then methoxy-acetic acid methyl ester (0.97 mL, 9.8 mmol) dissolved in anhydrous THF (10 mL) was added dropwise and stirring was continued at −78° C. for 2 h. At completion of the reaction, monitored by TLC, saturated NaHCO3 was added with vigorous stirring. The quenched mixture was extracted with EA (2×20 mL) and the combined organic extracts were washed with saturated NaHCO3 (20 mL) and dried over Na2SO4. The residue was purified by flash chromatography on silica gel with EA/hexane to provide the title compound as a colorless oil. MS (m/z): 300.5 [M+H+].

1. additionwas added dropwise
2. additionwas added dropwise
3. stirringstirring
4. waitwas continued at −78° C. for 2 h
5. customAt completion of the reaction
6. additionwas added with vigorous stirring
7. extractionThe quenched mixture was extracted with EA (2×20 mL)
8. washthe combined organic extracts were washed with saturated NaHCO3 (20 mL)
9. dry with materialdried over Na2SO4
10. customThe residue was purified by flash chromatography on silica gel with EA/hexane

ORD record

ord-00e94146245944e0907b4e3c7a36cfe1

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08410134B2