Regioselective Addition of Grignard Reagents to the 1-Phenoxycarbonyl Salts of Alkyl Nicotinates

Thermodynamic characteristics of NADH/NAD+ analogues in acetonitrile: 2-methyl, 4-methyl and 2,4-dimethyl 1-benzyl-dihydronicotinamides and the corresponding pyridinium species

“…A mixture of 1 (12.1 g, 88 mmol), cuprous iodide (762 mg, 3.8 mmol), and methyl sulfide (17.6 mL) was treated with phenyl chloroformate (10.4 mL, 80 mmol) in 200 mL of THF at -20°C (Dry Ice -CCl,) followed by addition of a 3 M solution of methyl magnesium chloride (90 mmol) in 30 mL of THF. Details of the reaction and work-up of the solution were similar to those reported in the literature (7). The crude methyl l-phenacyl-4-methyl-1 4-dihydronicotinate was aromatized with sulfur (3 g, 171 mmol) in refluxing decalin (1 10 mL, 3 h).…”

“…Therefore, to circumvent this problem, we devised a simple and handy method starting with the commercially available methylnicotinate 1 (Scheme 1). Compound 1 activated by reaction with phenyl chloroformate was converted into its corresponding methyl 4-methylnicotinate according to a very convenient two-step procedure described in the literature (7). The copper-catalyzed regioselective addition of the methyl Grignard reagent to the phenoxycarbonyl salt of 1 followed by aromatization of the crude 4-methyl-l,4-dihydropyridine afforded, at the 0.1 mol scale, the 4-methylated ester in an overall yield of 40%.…”

“…In the presence of the substrate AiH, the anodic current increases. The value of the ratio iJipO of the oxidation peak currents in the presence and absence of AiH, respectively, is a reflection of the kinetics of the reactions following step [7]. The mediators used were selected so that their standard potentials were close enough to the oxidation potential of AiH to obtain an appreciable increase in current and not too close, so as to avoid overlapping of the catalytic and direct oxidation waves (5e, 12).…”

“…Work-up of the solution was analogous to that described in ref. 7. The isolated crude methyl 4-methylnicotinate (5.1 g), obtained as a brown oil, was reacted with concentrated aqueous ammonia (20 mL, 4 days) in a classical manner (15).…”

Synthesis and Analgesic Activity of 2-Methyl-2-[1-(3-benzoyl-4-substituted-1,4-dihydropyridyl)]acetic Acid Methyl Esters, Acetic Acids, and Acetamides

“…Thus, reaction of the 3-benzoylpyridine compound (5, R 1 = H, Cl, Me) with racemic methyl 2-bromopropionate in acetone at reflux temperature afforded the corresponding pyridinium bromide salt (6). The subsequent regiospecific copper-catalyzed reaction [5] of a Grignard reagent (R 2 MgCl; R 2 = Ph, 4-Cl-C 6 H 4 -, 4-Me-C 6 H 4 -, cyclohexyl, PhCH 2 , n-Bu, i-Bu, n-hexyl, A group of 2-methyl-2-[1-(3-benzoyl-4-substituted-1,4-dihydropyridyl)]acetic acid methyl esters (7), weak acetic acids (8), and acetamides (9) were designed for evaluation as less acidic non-ulcerogenic non-steroidal antiinflammatory drugs (NSAIDs).…”