1,3-Cyclohexanedione → Ethyl 2-(4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetate

Temperature

190 °C

To a solution of cyclohexane-1,3-dione (50.7 g, 452 mmol) in N,N-dimethylformamide (700 mL) was added ethyl hydrazinoacetate hydrochloride (70 g, 452 mmol). The reaction mixture was stirred for 5 minutes before addition of dimethoxymethyl-dimethyl-amine (53.9 g, 452 mmol). The reaction mixture was divided into 50 vials, which were heated in a microwave at 190° C. for 2 minutes. After cooling to room temperature, the combined reaction mixture was concentrated in vacuo to remove most of the N,N-dimethylformamide. Water (200 mL) was added, and the resulting dark brown mixture was extracted with ethyl acetate (200 mL×3). The organic layers were combined, washed with brine (600 mL), dried over sodium sulfate and concentrated in vacuo to afford a brown oil, which was placed in a fridge overnight. The resulting yellow precipitate was filtered and washed with petroleum ether to give (4-oxo-4,5,6,7-tetrahydro-indazol-1-yl)-acetic acid ethyl ester (79 g, 79%) as yellow crystals. 1H NMR (400 MHz, CDCl3) δ ppm 7.92 (s, 1H), 4.89 (s, 2H), 4.26 (m, 2H), 2.80 (t, J=6.4 Hz, 2H), 2.51 (t, J=6.4 Hz, 2H), 2.20 (t, J=6.4 Hz, 2H), 1.31 (t, J=7.2 Hz, 3H). MS calcd. for C11H14N2O3 222, obsd. (ESI+) (M+H)+223.

1. temperatureAfter cooling to room temperature
2. customthe combined reaction mixture
3. concentrationwas concentrated in vacuo
4. customto remove most of the N,N-dimethylformamide
5. additionWater (200 mL) was added
6. extractionthe resulting dark brown mixture was extracted with ethyl acetate (200 mL×3)
7. washwashed with brine (600 mL)
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated in vacuo
10. customto afford a brown oil, which
11. filtrationThe resulting yellow precipitate was filtered
12. washwashed with petroleum ether

ORD record

ord-f62fecccd306472daf7054c34b29d0c6

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268870B2