Hydrochloric Acid → Boc-cyclohexylalanine

Participants

Reaction Steps

Boc-Cyclohexylalanine-Dicyclohexylamine salt (0.497 g, 1.1 mM) was added to a mixture of ethyl acetate (25 ml) and 0.5 N HCl (25 ml) for 30 minutes. The ethyl acetate layer was separated, washed with water (3×100 ml), dried over MgSO4, and evaporated to give the Boc-Cyclohexylalanine free acid (1.1 mM). The acid was dissolved in 25 ml of THF and cooled to 5° C. under N2. The acid was converted into a mixed anhydride by treatment with N-methyl morpholine (100 ul, 1 mM) and Isobutylchloroformate (130 ul, 1 mM). After stirring for 20 minutes, a solution of a racemic mixture of 2-(R)-3(S)-(1H-5-imidazoyl)-cyclopropylamine and 2-(S)-3(R)-(1H-5-imidazoyl)-cyclopropylamine (200 mgs, 1 mM) and triethylamine (284 u., 2 mM) in 2 ml of water was added. After 2 hours, the reaction mixture was portioned between ethyl acetate (50 ml) and water (50 ml), the ethyl acetate layer was washed with saturated sodium bicarbonate solution, water, then dried over sodium sulfate, filtered, and evaporated in vacuo to give the BOC protected amine of L-Cyclohexylalanine amide of 3(S)-(1H-5-imidazoyl)-2(R)-cyclopropylamine and its diasterisomer, the L-Cyclohexylalanine amide of 3(R)-(1H-5-imidazoyl)-2(S)-cyclopropylamine. The BOC group was deprotected by treating the crude amides directly with Trifluoroacetic acid (5 ml) for 30 minutes at r.t. The TFA was evaporated, and the residue triturated with ether to provide the ditrifluoroacetic acid salt and the diastereisomeric mixture of (1R,2R)trans-2-(S)-amino-3-(cyclohexyl-N-(2-imidazol-4-ylcyclopropyl)propanamide and (1S,2S)-trans-2-(S)-amino-3-cyclohexyl-N-(2-imidazol-4-ylcyclopropyl)propanamide (300 mgs). The diastereoisomers were separated using reverse phase HPLC.

Provenance & Evidence