Nitric Acid → 7-nitro-2,3-dihydro-1H-imidazo[1,2-b]pyrazole

To a solution of 2,3-dihydro-1H-pyrazolo[1,5-a]imidazole (1 g, 9.17 mmol) in conc. H2SO4 (aq.) at 0° C. was added conc. HNO3 (aq.) portion-wise over 15 min. The reaction was warmed to room temperature and the mixture was stirred for 18 h. The mixture was poured into ice water (200 mL) with stirring. The product was extracted into DCM and the combined organics were washed with saturated aqueous NaHCO3. The organic layer was separated, passed through a phase separator cartridge and concentrated under reduced pressure. The crude residue was triturated with diethyl ether to yield 7-nitro-2,3-dihydro-1H-pyrazolo[1,5-a]imidazole as a pale brown solid (0.52 g, 34%). Sodium hydride (60% dispersion in mineral oil, 0.065 g, 1.62 mmol) was added in 2 portions to a stirred solution of 7-nitro-2,3-dihydro-1H-pyrazolo[1,5-a]imidazole (0.21 g, 1.35 mmol) in anhydrous DMF (10 mL) at room temperature under a nitrogen atmosphere. The mixture was stirred for 10 min. before di-tert-butyl dicarbonate (0.68 mL, 2.75 mmol) was added. The reaction was stirred for 45 min. Water (5 mL) was added dropwise and the mixture concentrated under reduced pressure. The residue was diluted with water and the product extracted into diethyl ether. The combined organics were dried over MgSO4 and concentrated under reduced pressure. The crude residue was purified via silica gel chromatography (0-100% EtOAc/isohexane) to give tert-butyl 7-nitro-2,3-dihydro-1H-pyrazolo[1,5-a]imidazole-1-carboxylate as a grey solid (0.22 g, 63%). 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 4.60-4.53 (m, 2H), 4.38-4.30 (m, 2H), 1.50 (s, 9H)

1. stirringwith stirring
2. extractionThe product was extracted into DCM
3. washthe combined organics were washed with saturated aqueous NaHCO3
4. customThe organic layer was separated
5. concentrationconcentrated under reduced pressure
6. customThe crude residue was triturated with diethyl ether

ORD record

ord-43fd9f17c7c34113b90456e1d700854a

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436001B2