Pyridine → HCID 11020867, compound

Participants

Reaction Conditions

Reaction Steps

A mixture containing methyl 3,4-dibromo-1-naphthoate (126 mg, 0.366 mmol), copper (I) cyanide (618 mg, 6.89 mmol), pyridine (0.1 mL), and dry N-methylpyrrolidinone (2.0 mL) was heated at approximately 150° C. for 1 h. cooled to room temperature, diluted with water, NH4OH and EtOAc. The mixture was stirred briefly and filtered. The organic phase was separated and the aqueous phase extracted with additional EtOAc. The combined organic extracts were washed (dilute aqueous NH4OH and saturated NaHCO3). dried (Na2SO4), filtered, and EtOAc was removed in vacuo. The products were separated by chromatography (5-15% EtOAc in hexane and hexane:DCM (2:1)) to afford methyl 3,4-dicyano-1-naphthoate (22 mg; 25%) [1H NMR (CDCl3) δ 9.01 (m, 1H), 8.41 (m, 1H), 8.36 (s, 1H), 7.9 (m, 2H), 4.08 (s, 3H); MS (EI) m/z 236 (M)], methyl 3-bromo-4-cyano-1-naphthoate (21.9 mg; 20.6%) [1H NMR (CDCl3) δ 8.86 (m, 1H), 8.31 (s, 1H), 8.28 (m, 1H). 7.75 (m, 2H), 4.05 (s, 3H); MS (EI) m/z 289 (M).], and methyl 4-bromo-3-cyano-1-naphthoate (28.3 mg; 26.6%) [1H NMR (CDCl3) δ 9.02 (m, 1H), 8.43 (m, 1H), 8.28 (s, 1H), 7.8 (m, 2H) 4.04 (s, 3H); MS (EI) m/z 289 (M)]. The esters were separately saponified by stirring with 1.1-1.2 equivalents of LiOH in THF:water:methanol (20:10:1) at room temperature. The solutions were concentrated in vacuo, diluted with additional water, acidified with 1N HCl, extracted with EtOAc, dried (Na2SO4), filtered, and the EtOAc was removed in vacuo to afford the individual carboxylic acids. Prior to use, the 3,4-dicyano-1-naphthoic acid was further purified by chromatography (10-20% methanol in DCM) to afford the title compound (15.3 mg, 87%) as an off-white solid. MS (EI) m/z 222 (M).

Provenance & Evidence