Hydrochloric Acid → HCID 22414788, compound

Participants

Reaction Conditions

Reaction Steps

In a 12 L round bottom flask, equipped with internal thermometer, mechanical stirrer, addition funnel and septum inlet, is placed a solution of 3,3-dimethylacryloylchloride (146 g, 1.23 mol) in CH2Cl2 (1000 mL). The stirred solution is cooled in a CH2Cl2 -dry ice bath to -10° C., and then TiCl4 (1M in CH2Cl2, 1476 mL, 1.47 mol, 1.2 eq) is added via canula at a rate such that the reaction mixture does not warm above -5° C. The solution is stirred for 10 min after addition is complete, and then a solution of 2,6-di-tert-butylphenol (253.4 g, 1.23 mol, 1.0 eq) in CH2Cl2 (500 mL) is added dropwise via addition funnel. The rate of addition is adjusted to maintain the reaction temperature below 0° C. After addition is complete, the cold bath is removed, and the mixture is allowed to stir at ambient temperature for 4 h. TLC analysis (EtOAc:hexane, 1:9) indicates the reaction to be complete. H2O (2 L) is added carefully, and the mixture is transferred to a 6 L extraction funnel. The organic phase is separated, washed with additional H2O (2×1000 mL), dried over Na2SO4, filtered, and returned to the 12 L reaction vessel. Ethereal HCl (1M, Aldrich, 2000 mL) is added. After stirring 2 h, the solution is transferred to the 6 L separatory funnel, and washed with H2O (3×1 L). The organic phase is dried over Na2SO4, filtered into a 10-L round bottom flask, and rotary evaported. The residue is taken up in 1 L pentane, and kept at -4° C. overnight. The resulting crystalline solid is filtered off and dried to give 3-chloro-1-(3, 5-di-tert-butyl-4-hydroxyphenyl )-3-methylbutan-1-one.

Provenance & Evidence