2-(BROMOMETHYL)-1,3,5-TRIMETHYLBENZENE

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1 (0.33 g, 1.5 mmol), TEA (0.209 mL, 1.5 mmol) and 2,4,6-Trimethylbenzylbromide (0.253 g, 1.5 mmol) were dissolved in 10 mL of EtOH and kept under reflux overnight. The solvent was removed and the remaining oil was purified by flash-chromatography on silica gel, applying a CHCl3/MeOH gradient. under reflux overnight The solvent was removed the remaining oil was purified by flash-chromatography on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-amino-3-hydroxy pyridine (29.6 g, 0.269 mol), dichloromethane (200 ml) and 40% aqueous sodium hydroxide solution (200 ml) was stirred for five minutes, then 2,4,6-trimethylbenzyl bromide (50 g, 0.296 mol) and Adogen 464 (5 ml) were added and stirring continued for 16 hours. The mixture was diluted with water and extracted with dichloromethane. Drying and evaporation of the organic extracts, and trituration with ether gave the desired product. Yield 29.6 g (41%), m.p. 160°-166 ° C. stirring continued for 16 hours extracted with dichloromethane Drying evaporation of the organic extracts, and trituration with ether

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A dry 250 ml flask is filled with 6.6 g (152 mmol) of sodium hydride in mineral oil emulsion (55%). Dry dimethylformamide (10 ml) is added and the mixture is cooled to 0° C. To this mixture bromomethylmesitylene (32.4 g, 152 mmol) in dry DMF (20 ml) is added. Compound of example 9 (10 g, 39 mmol) is dissolved in dry DMF (20 mL) and added very to the above mixture over 40 minutes. After an additional hour the ice-bath is removed and the reaction is stirred at room temperature for 21 hours. Methanol (15 ml) is added to quench and the reaction mixture is stirred for another hour, then it is diluted with ethyl acetate (200 ml) and extracted with sat. NaHCO3 (200 ml), 1N HCl (200 ml), water (200 ml) and brine (200 ml). The title compound is obtained after column chromatography purification and crystallization. added very to the above mixture over 40 minutes After an additional hour the ice-bath is removed Methanol (15 ml) is added to quench the reaction mixture is stirred for another hour it is diluted with ethyl acetate (200 ml) extracted with sat. NaHCO3 (200 ml), 1N HCl (200 ml), water (200 ml) and brine (200 ml)