Hydrochloric Acid → ethyl 2-(5-(3-(hydroxymethyl)pyridin-2-yl)-1H-pyrazol-1-yl)acetate

Temperature

80 °C

To (E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one (crude, 350 mg, 1.09 mmol, 1 eq.) in EtOH (10 mL) was added ethyl 2-hydrazinylacetate hydrochloride (338 mg, 2.18 mmol, 2.0 eq.). The mixture was heated at 80° C. for 2 h, cooled to rt, added HCl (6 N, 0.5 mL), and stirred O/N. The mixture was concentrated, and diluted with a mixture of EtOAc (50 mL) and NaHCO3(sat) (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using EtOAc as eluent to give ethyl 2-(5-(3-(hydroxymethyl)pyridin-2-yl)-1H-pyrazol-1-yl)acetate (212 mg, 74%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.61 (dd, J=4.7, 1.6 Hz, 1H), 7.97 (dd, J=7.8, 1.4 Hz, 1H), 7.64 (d, J=1.9 Hz, 1H), 7.36 (dd, J=7.8, 4.8 Hz, 1H), 6.56 (d, J=1.9 Hz, 1H), 5.21 (s, 2H), 4.79 (d, J=5.8 Hz, 2H), 4.09 (q, J=7.1 Hz, 2H), 2.54 (t, J=6.0 Hz, 1H), 1.18 (t, J=7.1 Hz, 31-1). LRMS m/z 262.1

1. temperaturecooled to rt
2. concentrationThe mixture was concentrated
3. additiondiluted with a mixture of EtOAc (50 mL) and NaHCO3(sat) (10 mL)
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with EtOAc three times
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated
8. custompurified on silica gel

ORD record

ord-14644d98923940b09b36899bdbb853ab

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012450B2