Water → HCID 90010077, compound

Method-1: To a 0° C. cooled solution of ethyl-5,6-dibromonicotinate (1.0 g, 3.24 mmol, 1.0 eq., prepared by following the procedure described in WO2011024004) in THF (10 mL) was added [1,3-bis(diphenylphosphino)propane]dichloronickel (II) (351 mg, 0.65 mmol, 0.2 eq) and the solution was stirred for 5 min. Ethyl magnesium bromide (1M in THF, 3.88 mL, 3.88 mmol, 1.2 eq) was then added drop-wise to the above mixture at 0° C. The resulting mixture was continued to stir at the same temperature for 3 h. Water (10 mL) was then added to the above mixture, followed by ethyl acetate (20 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×10 mL) and the combined organic layers were washed with brine (20 mL), dried (Na2SO4) and filtered. The filtrate was evaporated and the crude residue was purified by flash column chromatography (silica gel, diethyl ether-hexane system as eluent) to afford 500 mg (60%) of the desired product as a white solid. 1HNMR (400 MHz, CDCl3) δ 9.06 (d, J=1.5 Hz, 1H), 8.40 (d, J=1.5 Hz, 1H), 4.42 (q, J=7.0 Hz, 2H), 3.05 (q, J=7.0 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H), 1.28 (t, J=7.0 Hz, 3H); GC-MS (m/z) 257, 259 [M+, Br79, 81].

1. customprepared
2. stirringto stir at the same temperature for 3 h
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with ethyl acetate (2×10 mL)
5. washthe combined organic layers were washed with brine (20 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customThe filtrate was evaporated
9. customthe crude residue was purified by flash column chromatography (silica gel, diethyl ether-hexane system as eluent)

ORD record

ord-570daaafa1ba4ba0b2f4ed036ae2e240

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09399638B2