Hydrochloric Acid → Amino-2-hydroxy-5-methylhexyl benzyl ether

HRID 1905328Notes

Reaction equation

HRID 1905328 reaction equation
C1(CC(CC(=O)NCCC2C=CC=CC=2)C([N:15](C(=O)[C@H](CC2N=CNC=2)N)N)=O)C2C(=CC=CC=2)C=CC=1.Cl.C1(CC(CC(=O)NCCC2C=CC=CC=2)C(N[C@H](C(N=[N+]=[N-])=O)CC2N=CNC=2)=O)C2C(=CC=CC=2)C=CC=1.[N-]=[N+]=[N-].Cl.[CH2:83]([O:90][CH2:91][CH:92]([OH:99])[C@@H:93](N)[CH2:94][CH:95]([CH3:97])[CH3:96])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1.C(=O)(O)[O-].[Na+]>CN(C)C=O.N(OCCC(C)C)=O.C(N(CC)CC)C>[CH2:83]([O:90][CH:91]([NH2:15])[CH:92]([OH:99])[CH2:93][CH2:94][CH:95]([CH3:97])[CH3:96])[C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][CH:85]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 33558AzideHCID 516892Sodium BicarbonateHCID 131715985(2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl benzyl ether hydrochlorideHCID 178511798HCID 178511798, compoundHCID 178514640HCID 178514640, compound

Product 1

HCID 131715987Amino-2-hydroxy-5-methylhexyl benzyl ether

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent3×HCID 8053Isoamyl NitriteSolventHCID 8471TriethylamineSolvent2×

Procedure

To a suspension of 31 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 1 ml of N,N-dimethylformamide were added successively dropwise 0.044 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.011 ml of isoamyl nitrite, and the mixture was stirred. After disappearance of hydrazide compound, the reaction mixture was cooled to +30° C., and neutrlized by adding 0.031 ml of triethylamine to prepare a solution of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)-propionyl]-L-histidine azide. The azide solution prepared was added dropwise to a solution of 16 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl benzyl ether hydrochloride and 0.011 ml of triethylamine in 1 ml of N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours under ice-cooling. A 5% aqueous sodium bicarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatograpy (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume) to obtain 18 mg of (2RS, 3S)-3-{N-(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexyl benzyl ether as a white powder.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by preparative silica gel thin layer chromatograpy (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume)

Sources & evidence

ORD record
ord-e4e36ccbbe874758b7ef1539d6f9300b
Source dataset
uspto-grants-1989_06
Patent number
US04841067

Reaction notes

Loading…