Hydrochloric Acid → HCID 178491557, compound

HRID 1608444Notes

Reaction equation

HRID 1608444 reaction equation
Cl.[N+]([O-])(OCCC(C)C)=O.[CH3:11][O:12][C:13]1[CH:35]=[CH:34][C:16]([CH2:17][O:18][C:19]([NH:21][C@H:22]([C:29]([N:31]=[N+]=[N-])=[O:30])[CH2:23][C:24]2[N:28]=[CH:27][NH:26][CH:25]=2)=[O:20])=[CH:15][CH:14]=1.[N-]=[N+]=[N-].[CH:39]([O:42][C:43](=[O:55])[CH:44]([OH:54])[C@@H:45](N)[CH2:46][CH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1)([CH3:41])[CH3:40]>CN(C)C=O.C(N(CC)CC)C>[CH:39]([O:42][C:43](=[O:55])[CH:44]([OH:54])[C@@H:45]([NH:31][C:29](=[O:30])[C@H:22]([CH2:23][C:24]1[N:28]=[CH:27][NH:26][CH:25]=1)[NH:21][C:19]([O:18][CH2:17][C:16]1[CH:34]=[CH:35][C:13]([O:12][CH3:11])=[CH:14][CH:15]=1)=[O:20])[CH2:46][CH:47]1[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52]1)([CH3:41])[CH3:40]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10985Isoamyl nitrateHCID 33558AzideHCID 14014853HCID 14014853, compoundHCID 178491559HCID 178491559, compound

Product 1

HCID 178491557HCID 178491557, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8471TriethylamineSolvent

Procedure

In 15 ml of N,N-dimethylformamide was suspended 1.37 g of the hydrazide compound, and to the suspension were successively added a solution of a 5.95N-dry hydrogen chloride in 2.29 ml of N,N-dimethylformamide and 0.66 ml of isoamyl nitrate with stirring at -20° C. After disappearance of the hydrazide compound, the reaction mixture was cooled to -30° C., and then neutralized by an addition of 1.89 ml of triethylamine to prepare a cold solution of N-(4-methoxybenzyloxycarbonyl)-L-histidine azide. The cold azide solution was added to a solution of 1.00 g of (2RS, 3S)-3-amino-4-cyclohexyl-2-hydroxybutyric acid isopropyl ester in 40 ml of N,N-dimethylformamide with stirring under ice-cooling. The mixture was still stirred for 16 hours, and then the reaction mixture was evaporated under reduced pressure. To the residue was added a 5% aqueous sodium bicarbonate solution, 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 silica gel flash column chromatography (eluent: chloroform/methanol=15/1) to obtain 1.70 g of (2RS, 3S)-3-[N-(4-methoxybenzyloxycarbonyl)-L-histidyl]amino-4-cyclohexyl-2-hydroxybutyric acid isopropyl ester as a white powder. In 50 ml of methanol was 1.70 g of the butyric acid isopropyl ester compound, and to the solution were added 10 ml of a 2N hydrochloric acid and 200 mg of a 10% palladium charcoal. The mixture was hydrogenated under an atmospheric pressure. After filtration of the catalyst, the filtrate was evaporated under reduced pressure to obtain 1.36 g of (2RS, 3S)-3-(L-histidyl)amino-4-cyclohexyl-2-hydroxybutyric acid isopropyl ester dihydrochloride as a white powder.

Workup

  1. temperaturecooling
  2. stirringThe mixture was still stirred for 16 hours
  3. customthe reaction mixture was evaporated under reduced pressure
  4. additionTo the residue was added a 5% aqueous sodium bicarbonate solution
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customevaporated under reduced pressure
  9. customThe residue was purified by silica gel flash column chromatography (eluent: chloroform/methanol=15/1)

Sources & evidence

ORD record
ord-432fcd846ada4ec49d3f7fcbbd0c4e70
Source dataset
uspto-grants-1989_09
Patent number
US04870183

Reaction notes

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