Hydrogen Bromide → HCID 86740228, compound

Participants

Reaction Steps

After an unsuccessful attempt to effect deprotection by catalytic hydrogenation under pressure (25 p.s.i.g.) with palladium on carbon as catalyst and acetic acid as solvent, a solution of (N-benzyloxycarbonyl-N-methyl-O-benzyl-L-tyrosyl)-N2 -methyl-N-(3-phenylpropyl)-D-alaninamide (1.7 g.) and hydrogen bromide in acetic acid (32%, 20 ml.) was allowed to stand at room temperature for one hour, then partially stripped of volatiles. Ether (100 ml.) was added to the residue, which was triturated three more times with ether, affording a yellow-brown oil. Upon reverse phase high pressure liquid chromatography on octadecylsilated silica gel (350 g.) using ammonium acetate (0.2%) in methanol-water (1:1) as the eluant, the product appeared in the methanol wash. Rechromatography using ammonium acetate (0.15%) in methanol-water (3:2) as the eluant and washing the residue of fractions 3-4 corresponding to k'=2.4-5.0 free of salt gave a beige gum (570 mg.). A solution of the beige gum in methanol-water (2:1) was passed through an ion exchange resin in the dihydrogen phosphate ion form, filtered and lyophilized, affording as an amorphous white solid N-methyl-L-tyrosyl-N2 -methyl-N-(3-phenylpropyl)-D-alaninamide phosphate (1:1) salt dihydrate (584 mg.; [α]D25 +61.6°, c=1, methanol), whose free base is the compound of Formula II wherein R1 and R2 are each methyl and R4 is (CH2)nY wherein n is 3 and Y is phenyl.

Provenance & Evidence