Hydrogen Bromide → HCID 86740228, compound

HRID 484928Notes

Reaction equation

HRID 484928 reaction equation
C(O[C:9]([N:11](C)[C@H:12]([C:28]([N:30]([CH3:45])[C@@H:31]([C:33]([NH:35][CH2:36][CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:34])[CH3:32])=[O:29])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20]CC2C=CC=CC=2)=[CH:16][CH:15]=1)=O)C1C=CC=CC=1.Br.C([O-])(=O)C.[NH4+].[P:53]([O-:57])([OH:56])([OH:55])=[O:54]>[Pd].C(O)(=O)C.CO.O.CO.CCOCC>[P:53]([OH:57])([OH:56])([OH:55])=[O:54].[CH3:9][NH:11][C@H:12]([C:28]([N:30]([CH3:45])[C@@H:31]([C:33]([NH:35][CH2:36][CH2:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:34])[CH3:32])=[O:29])[CH2:13][C:14]1[CH:15]=[CH:16][C:17]([OH:20])=[CH:18][CH:19]=1

Participants

10

Reactant 4

HCID 260Hydrogen BromideHCID 1003DihydrogenphosphateHCID 517165Ammonium AcetateHCID 86740230HCID 86740230, compound

Product 1

HCID 86740228HCID 86740228, compound

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent2×HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 22242641Methanol--water (1/1)Solvent2×

Procedure

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.

Workup

  1. customwas triturated three more times with ether
  2. customaffording a yellow-brown oil
  3. washwash
  4. washwashing the residue of fractions 3-4 corresponding
  5. customgave a beige gum (570 mg.)
  6. filtrationfiltered

Sources & evidence

ORD record
ord-582fc94451ff4c95a2113107b5790237
Source dataset
uspto-grants-1985_08
Patent number
US04533655

Reaction notes

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