Lithium Hydroxide → Methyl 6-(4-chlorophenyl)-2,2-dimethyl-4-oxohexanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl (4-chlorobenzene)-propanoate (Step B, 10 g) in dry THF (500 mL) at -78° C. was added 0.58M potassium hexamethyldisilazane in toluene (243 mL). The mixture was stirred at -60° C. for one hour. Then a solution of 2,2-dimethylsuccinic anhydride (6 g) in THF (100 mL) was added slowly and the mixture was slowly warmed to room temperature and finally stirred for 18 hours. Water (1000 mL) was added and the organic layer separated, The aqueous layer was washed with EtOAc (3×250 ml) and acidified with 1N HCl. The aqueous layer was extracted with EtOAc, the extract was dried (Na2SO4) and evaporated to give a residue which was dissolved in THF (100 mL) and MeOH (200 mL) and treated at reflux with 1N LiOH (100 mL) for 4 hours. The mixture was cooled to room temperature and concentrated under vacuum until H2O distilled off. Water (500 mL) was added, the mixture acidified with 1N aq. HCl, extracted with EtOAc, the extract was dried (Na2SO4) and evaporated to give the title product as its carboxylic acid. The compound was treated with diazomethane in ether, evaporated to dryness and chromatographed over silica gel, eluting with EtOAc-hexane (10:90) to give the title product as a white solid; m.p. 52°-54° C.

Provenance & Evidence