Water → 4-Hydroxy-1,5-dimethyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acid

Temperature

-40 °C

To a solution of LiHMDS (331 mL, 331 mmol, 1 M solution in THF) in THF (430 mL) at −78° C. was added a solution of 2-(2-methyl-2-propionylhydrazono)malonate (21.40 g, 82.86 mmol) in THF (10 mL). The resulting mixture was slowly warmed to −40° C. over 1 hour and stirred for 1.5 hours at −40° C. To the reaction mixture was added water (500 mL) at −40° C. The reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was concentrated under reduced pressure, quenched with 6 N aqueous HCl at 0° C., and acidified to pH 1 to 2. The resulting mixture was stirred for 16 hours at room temperature. The precipitates were filtered off and triturated with CH2Cl2 to afford 7.21 g (47%) of the desired product. The filtrate was extracted with EtOAc (3×). The combined organic layers were washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was triturated with CH2Cl2 to afford additional 3.56 g (23%) of the desired product. The aqueous layer was extracted again with EtOAc (3×). The combined organic layers were washed with water, dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was triturated with CH2Cl2 to afford additional 1.32 g (9%) of the desired product. A total of 12.09 g (79%) of the desired product was obtained.

1. temperatureThe reaction mixture was warmed to room temperature
2. stirringstirred for 3 hours
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. customquenched with 6 N aqueous HCl at 0° C.
5. stirringThe resulting mixture was stirred for 16 hours at room temperature
6. filtrationThe precipitates were filtered off
7. customtriturated with CH2Cl2

ORD record

ord-90412fc8824647fdaa914ec24b53a38a

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299076B2