65515-39-1

General procedure for the synthesis of 2-methoxy-4,6-dimethylnicotinonitrile from 2-chloro-3-cyano-4,6-dimethylpyridine and sodium methanol: A methanolic solution of sodium methanol (30 mass %, 175 mL, 940 mmol) was added slowly and dropwise to a methanolic solution (450 mL) of 2-chloro-4,6-dimethylpyridine-3-carbonitrile (75 g, 441.1 mmol) The reaction was carried out in a water bath. Subsequently, a methanolic solution of sodium methanolate (25 mass %, 250 mL, 1090 mmol) was added dropwise. The reaction mixture was stirred for 1 hour and then poured into ice water and continued to stir for 30 minutes and the solid product was collected by filtration. The filter cake was washed with hexane and dried in a vacuum oven overnight. The aqueous phase filtrate was extracted with dichloromethane and the organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The solid obtained by filtration was combined with the concentrated residue to give 2-methoxy-4,6-dimethylnicotinonitrile as a solid product (71.8 g, quantitative yield). Electrospray mass spectrometry (ES/MS) showed m/z: 163 ([M+H]+).

[1] Patent: WO2017/35060, 2017, A1. Location in patent: Page/Page column 48; 49
[2] Patent: WO2005/63768, 2005, A1. Location in patent: Page/Page column 33-34
[3] Patent: WO2005/97750, 2005, A1. Location in patent: Page/Page column 75
[4] Journal of the American Chemical Society, 1949, vol. 71, p. 331