Water → Ethyl 2-(hydroxymethyl)pyrazolo[1,5-A]pyrimidine-6-carboxylate

Temperature

0 °C

Ethyl 2-formyl-3-oxopropionate (775 mg) was added to a solution of the thus obtained 5-methoxymethyl-2H-pyrazol-3-ylamine (684 mg) in ethanol (50 ml), and stirred overnight. The reaction solution was concentrated under reduced pressure, and a saturated sodium bicarbonate solution was added to the residue which were then extracted with ethyl acetate. The organic phase was washed with a saturated saline solution and dried over sodium sulfate anhydrous. The resulting product was concentrated under reduced pressure, and the residue was purified by column chromatography (eluting solvent; n-hexane:ethyl acetate 4:1) to give ethyl 2-methoxymethylpyrazolo[1,5-a]pyrimidine-6-carboxylate (878 mg, Y.:69%). 1 M Boron tribromide solution in dichloromethane (0.51 ml) was added dropwise at −70° C. to a solution of the thus obtained ethyl 2-methoxymethylpyrazolo[1,5-a]pyrimidine-6-carboxylate (20 mg) in dichloromethane (2 ml). The temperature of the mixture under stirring was increased from −70° C. to −50° C. over 4.5 hours and then increased from −50° C. to room temperature over 2 hours. The reaction mixture was cooled to 0° C., water was added to the reaction mixture which was then extracted with ethyl acetate, and the extract was dried over sodium sulfate anhydrous. The resulting product was concentrated under reduced pressure to give ethyl 2-hydroxymethylpyrazolo[1,5-a]pyrimidine-6-carboxylate (19 mg, Y.:quant.).

1. temperaturewas increased from −70° C. to −50° C. over 4.5 hours
2. temperatureincreased from −50° C. to room temperature over 2 hours
3. extractionwas then extracted with ethyl acetate
4. dry with materialthe extract was dried over sodium sulfate anhydrous
5. concentrationThe resulting product was concentrated under reduced pressure

ORD record

ord-211a9e893dfc49a09aa8d957b20feec5

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07345180B2