Water → HCID 70136055, compound

Participants

Reaction Steps

3-(4-Methoxybenzoyl)-2-chlorotoluene (4.55 g, 17.45 mmol) [prepared by the method described in Example 1(a)]was dissolved in benzene (150 ml), and the solution was purged with nitrogen. N-Bromosuccinimide (3.10 g, 1 eq.) and benzoyl peroxide (0.42 g, 0.1 eq.) were added and the reaction mixture was heated at reflux overnight. Since there was an appreciable amount of unreacted starting material still present in the reaction mixture, additional amounts of N-bromosuccinimide (1.55 g, 0.5 eq.) and benzoyl peroxide (0.21 g, 0.05 eq.) were added, and the heating was continued. After 3 h the reaction mixture was cooled to room temperature, and diluted with ether. The organic layer was separated, washed with water and brine, and dried over MgSO4. The solvent was removed in vacuo to give 7.6 g of an orange oil. Purification by flash chromatography (10/90 EtOAc/hexanes) gave 3-(4-methoxybenzoyl)-2-chlorobenzyl bromide as an oil that slowly crystallized to a solid (5.13 g, 87% yield). 1H NMR showed it was approximately 90% pure 3-(4-methoxybenzoyl)-2-chlorobenzyl bromide (4.97 g, 1 eq.) [prepared as described above] was added to a solution of KCN (1.05 g, 1.1 eq.) in dry DMSO (40 ml) under a nitrogen atmosphere. After 30 min the reaction mixture was poured into water (1 L) and the product was extracted into ethyl acetate. The organic extract was washed with water and brine, and dried over MgSO4. The solvent was evaporated in vacuo to give 2-[3-(4-methoxy-benzoyl)-2-chlorophenyl]acetonitrile (4.08 g, 98% yield) as an oil.

Provenance & Evidence