Lithium Hexamethyldisilazide → Ethyl 4-hydroxy-1,5-dimethyl-6-oxo-1,6-dihydropyridazine-3-carboxylate

Temperature

-40 °C

To a solution of LiHMDS (0.78 mL, 0.78 mmol, 1 M solution in THF) in THF (1 mL) at −78° C. was added a solution of diethyl 2-(2-methyl-2-propionylhydrazono)malonate (50 mg, 0.19 mmol) in THF (1 mL). The resulting mixture was slowly warmed to −40° C. and stirred for 1.5 hours at −40° C. The reaction mixture was quenched with 10% aqueous HCl and diluted with water. The resulting mixture was extracted with EtOAc (2×). The combined organic layers were washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (100% hexanes to 20% EtOAc in hexanes) to afford 25 mg (61%) of the desired product.

1. customThe reaction mixture was quenched with 10% aqueous HCl
2. additiondiluted with water
3. extractionThe resulting mixture was extracted with EtOAc (2×)
4. washThe combined organic layers were washed with water
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto give the crude material that
9. customwas purified by silica gel flash column chromatography (100% hexanes to 20% EtOAc in hexanes)

ORD record

ord-ef0e6ec9ed3e401ba03bc678a049c003

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07732616B2