Diisopropylamine → Norvaline, 2-propyl-, ethyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 10.4 ml of diisopropylamine in 200 ml of tetrahydrofuran was combined dropwise at 0° C. with stirring under a stream of dry nitrogen with 49 ml of a 1.6 molar solution of n-butyllithium in n-hexane. After cooling to -78° C., a solution of 18.31 g of the product from stage 2 in 80 ml of tetrahydrofuran was added dropwise. The entire reaction batch was stirred for 30 minutes and a solution of 8.8 ml of 1-iodopropane in 40 ml of tetrahydrofuran was then added dropwise. The reaction batch was stirred for 16 hours, wherein the temperature slowly rose to 20° C. The solvent was removed by distillation. The resultant orange-coloured residue was redissolved in 500 ml of 1 N hydrochloric acid. After 1 hour's stirring at 20° C., extraction was performed three times with 100 ml portions of diethyl ether. The phase acidified with hydrochloric acid was adjusted to a pH of between 10 and 12 with potassium hydroxide and then extracted three times with 100 ml portions of diethyl ether. The extracts were combined, washed twice with a saturated sodium chloride solution and dried over sodium sulphate. The crude product obtained after removing the solvent by distillation was purified by passage through a silica gel column with ethyl acetate. 9.84 g of 2-amino-2-propylpentanoic acid ethyl ester (67% of th.) were obtained in the form of a slightly coloured oil.

Provenance & Evidence