Diethyl methylmalonate → 1-(3-bromophenyl)-5-hydroxy-4-methyl-1,2-dihydro-3H-pyrazol-3-one

Temperature

90 °C

To a suspension of 1-(3-bromophenyl)hydrazine hydrochloride (1.0 g, 4.47 mmol) in ethanol (8.9 mL) was added dropwise 2.0 M sodium ethoxide in ethanol (0.77 mL, 9.84 mmol, 2.2 eq.). Diethyl 2-methylmalonate (0.85 mL, 4.92 mmol, 1.1 eq.) was then added. The reaction mixture was stirred at 90° C. for 16 hours and then quenched with 2 N aqueous hydrochloric acid (50 mL). The reaction was extracted with ethyl acetate (3×50 mL), and the combined organic layers were dried (MgSO4), filtered, and evaporated under reduced pressure. Purification using MPLC (Biotage) eluted with 3:1 v/v ethyl acetate-hexane gave the desired product as a white solid (125 mg, 0.46 mmol, 10.4% yield). MS LC-MS (ES MH+=269/271); TLC (Rf=0.10, 50% ethyl acetate-hexane).

1. customquenched with 2 N aqueous hydrochloric acid (50 mL)
2. extractionThe reaction was extracted with ethyl acetate (3×50 mL)
3. dry with materialthe combined organic layers were dried (MgSO4)
4. filtrationfiltered
5. customevaporated under reduced pressure
6. customPurification
7. washeluted with 3:1 v/v ethyl acetate-hexane

ORD record

ord-c0a2637b7cfc4f828ad4965f769c119f

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06660752B2