Acetonitrile → 1H-Pyrazole-5-carboxylic acid, 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-, ethyl ester

To a 500 mL flask, acetonitrile (200 mL), ethyl 1-(3-chloro-2-pyridinyl)-3-oxopyrazolidine-5-carboxylate (21.28 g, 94%, 74.17 mmol) and phosphoryl bromide (14.88 g, 51.92 mmol) were added. The reaction mixture was heated to reflux for 2 hours. 150 mL solvent was distilled from the reaction mixture. The concentrated reaction mixture was added to the mixture of sodium carbonate (10.56 g, 155.7 mmol) and water (40 mL). The reaction mixture was stirred for 20 minutes until no more gas released, and then diluted with dichloromethane (100 mL), stirred for 50 minutes. The mixture was extracted with dichloromethane (3×200 mL). The combined organic layers were washed with water, dried over anhydrous magnesium sulfate, and concentrated by rotary evaporator to give ethyl 3-bromo-1-(3-chloro-2-pyridinyl)-4,5-dihydro-1H-pyrazole-5-carboxylate (25.73 g) as a amber oil in 97% yield. HPLC area normalization method content is 93% (Analytical condition: chromatographic column: ZORBAX Eclipse XDB-C8 4.6×150 mm 5 μm, mobile phase:the ratio of acetonitrile to water is 70:30).

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 2 hours
3. distillation150 mL solvent was distilled from the reaction mixture
4. customThe concentrated reaction mixture
5. stirringstirred for 50 minutes
6. extractionThe mixture was extracted with dichloromethane (3×200 mL)
7. washThe combined organic layers were washed with water
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated by rotary evaporator

ORD record

ord-11b215f9792b4822aa4c12615fc37ccf

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217179B2