Benzyl Alcohol → 2-(Benzyloxy)pyridine-4-carboxylic acid

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Reaction Steps

2-Chloro-isonicotinic acid [CAS Reg. No. 6313-54-8] (4 g) and benzyl alcohol (3.3 g) were added to dry toluene (50 mL). Sodium hydride (2.66 g, 50% in mineral oil) was added in 2 portions and the mixture was allowed to stir at room temperature for 30 minutes. 18-Crown-6 (906 mg) was added and the mixture was then heated to 125° C. for 12 hours. An unstirrable, yellow mixture was obtained. This was diluted with more toluene (80 mL) and stirring was continued for another 4 hours at 125° C. TLC analysis confirmed that there was still 2-chloro-isonicotinic acid left. More benzyl alcohol (3.3 g) and sodium hydride was (2.66 g) added and the mixture was heated for another 12 hours. The mixture was cooled and quenched with 1M aqueous HCl (100 mL). Hexane (200 ml) was added and the mixture was stirred at 0° C. for 1 hour; a light brown solid was obtained. The solid was filtered off and washed with hexane. To remove residual water from the solid, toluene was added and removed again. A colorless solid was obtained (4.8 g). MS (m/e, ISP neg ion): 228.3 (M−H+).

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