Dimethyl Sulfide → 4-Methyl-3-phenoxypyridine

Participants

Reaction Steps

To a solution of 3-phenoxypyridine (10.26 g, 0.06 mol) in dry THF (500 ml) under nitrogen was added copper(I) iodide and methyl sulphide (30 ml). The mixture was stirred at room temperature for 15 minutes and then cooled to -25° C. Phenyl chloroformate (8.0 ml, 0.066 mol) was then added dropwise to produce a dark-brown solution. After 10 minutes methylmagnesium bromide (20 mls of 3M solution, 0.066 mol) was added dropwise at -25° C. After stirring at -25° C. for 15 minutes the solution was warmed to room temperature over 1 hour, during which time the solution had become a clear light yellow colour. The reaction was quenched with 20% aqueous ammonium chloride solution (150 ml) and then partitioned with ether (250 ml). The organic layer was washed with 20 ml portions of 20% aqueous ammonium chloride--ammonium hydroxide (1:1) solution, 10% hydrochloric acid, water and brine. After drying the ether was evaporated to give a yellow oil which was redissolved in dry toluene (250 ml). A suspension of o-chloranil (15 g) in toluene (100 ml) was added portionwise at room temperature. The resulting dark solution was stirred overnight and then 10% aqueous sodium hydroxide solution (200 ml) was added and stirring continued for 10 minutes at room temperature. The reaction mixture was partitioned with ether (200 ml) and the organic layer washed with 200 ml portions of 10% aqueous sodium hydroxide solution and water and then 10% hydrochloric acid (4×250 ml). The acidic extracts were basified with 25% aqueous sodium hydroxide solution and then extracted with methylene chloride (X4). The combined methylene chloride extracts were dried and evaporated to give a yellow oil. Bulb-to-bulb distillation (100° C. at 0.05 mBar) afforded 3-phenoxy-4-methylpyridine (6.5 g) as a clear liquid, 1H NMR delta (CDCl13) 2.25 (3H,s); 6.9-7.4 (6H,m); 8.2 (1H,s); 8.3 (1H,d).

Provenance & Evidence