Glutaric anhydride → 4-(4-Fluorobenzoyl)butyric Acid

Participants

Reaction Conditions

Reaction Steps

Charged 260 g of anhydrous AlCl3 (1.87 moles) to a 2 L 3-neck round bottom flask, added 300 mL fluorobenzene (307.5 g; 3.2 moles) and cooled the mixture in an ice bath to 5° C. Added a hazy suspension of 100 g glutaric anhydride (0.86 mole) in 400 mL fluorobenzene (4.3 moles) through an addition funnel over a period of 45 min., and maintained the temperature below 12° C. The reaction mixture was warmed to ambient temperature gradually and agitated at r.t. for about 90 min.; checked for completion by NMR. Cooled the reaction mixture to 0 to 5° C., then added a cold aqueous solution (700 ml) of 1N HCl carefully to the mixture to destroy any unreacted AlCl3, keeping the temperature of the mixture below 20° C. during the early part of the acid addition, and below 40° C. for the rest of the time. Poured the entire mixture into a 2 L 1:1 mixture of water and ice (v/w) to precipitate out crude products, filtered the white suspension and washed well with water. Added the white residue to 3 L of aqueous saturated solution (˜5%) of NaHCO3, heated the basic mixture on a steam bath for one hour and filtered the batch while hot through a thin pad of celite. Cooled the filtrate to r.t., added about 320 mL of concentrated HCl dropwise into the filtrate to pH 1 to crystallize out products, and agitated the white suspension in an ice bath for 30 min. Filtered the batch, washed the wet cake with ice cold water and dried in a vacuum oven at 50° C. for 16 h to obtain 143.2 g of 4-(4-fluorobenzoyl)-butyric acid; m.p. 141 to 142° C., isolated yield: 79.3%.

Provenance & Evidence