Sodium hydride → Methyl 3-[(4-methoxy)-tetrahydropyran-4-yl]phenylmethoxyacetate

Temperature

5 °C

A solution of methyl glycolate (0.35 g, 3.9 mmol) in 5 mL of anhydrous DMF was added to a suspension of sodium hydride (0.11 g, 4.6 mmol) in 5 mL of anhydrous DMF at 5° C., and the reaction mixture was stirred for 40 minutes at 5° C. A solution of 3-[(4-methoxy)tetrahydropyran-4-yl]-α-bromotoluene (1 g, 3.9 mmol) in 10 mL of anhydrous DMF was added to the cold methyl glycolate solution while maintaining the temperature at 5° C. The mixture was stirred for 2 h at 5° C., then for 18 h at room temperature. The mixture was quenched with water (100 mL) and the aqueous solution was extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with saturated brine (1×100 mL), dried over magnesium sulfate, filtered and concentrated. The concentrated residue was purified by flash column chromatography on silica gel, eluting with 25% ethyl acetate in hexane, to give 0.57 g (50%) of methyl 3-[(4-methoxy)-tetrahydropyran-4-yl]phenylmethoxyacetate as a clear oil: HRMS calcd for C16H22O5 295.1545. Found 295.1502.

1. temperaturewhile maintaining the temperature at 5° C
2. stirringThe mixture was stirred for 2 h at 5° C.
3. waitfor 18 h at room temperature
4. customThe mixture was quenched with water (100 mL)
5. extractionthe aqueous solution was extracted with ethyl acetate (2×100 mL)
6. washThe combined organic extracts were washed with saturated brine (1×100 mL)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe concentrated residue was purified by flash column chromatography on silica gel
11. washeluting with 25% ethyl acetate in hexane

ORD record

ord-cbce66bd79d847dd94beec29adfabfee

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06998415B2