Toluene → tert-butyl 4,5-dihydro-1H-pyrazole-5-carboxylate

1,1-Dimethylethyl 2-propenoate (10.25 ml, 70 mmol) was added to a round-bottom flask equipped with a stirring bar and charged with toluene (100 ml) and tetrahydrofuran (THF) (100 ml) under nitrogen, and then TMS-diazomethane (42.0 ml, 84 mmol) was added. After 4 h, the reaction solvents and excess TMS-diazomethane were removed in vacuo. The residue was dissolved in dichloromethane (150 mL). TFA (6.26 ml, 84 mmol) was added at 0° C. and the resulting mixture was stirred at room temperature overnight. After this time, the reaction was quenched with sat. Na2CO3 and extracted with dichloromethane. The organic layer was dried over Na2SO4. The solvent was removed under reduced pressure to give the crude product as yellow oil, which was purified by silica gel chromatography (Combiflash, 120 g column, hexane/ethyl acetate 0-30% 60 min) to yield the desired product 1,1-dimethylethyl 4,5-dihydro-1H-pyrazole-5-carboxylate (9.7 g, 81% yield) as yellow oil.

1. customequipped with a stirring bar
2. customthe reaction solvents and excess TMS-diazomethane were removed in vacuo
3. dissolutionThe residue was dissolved in dichloromethane (150 mL)
4. customAfter this time, the reaction was quenched with sat. Na2CO3
5. extractionextracted with dichloromethane
6. dry with materialThe organic layer was dried over Na2SO4
7. customThe solvent was removed under reduced pressure
8. customto give the crude product as yellow oil, which
9. customwas purified by silica gel chromatography (Combiflash, 120 g column, hexane/ethyl acetate 0-30% 60 min)

ORD record

ord-ea89f3b48d054f98af23bf793efe5956

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901119B2