Hydrochloric Acid → HCID 178459632, compound

HRID 1608445Notes

Reaction equation

HRID 1608445 reaction equation
[CH:1]([O:4][C:5](=[O:39])[CH:6]([OH:38])[C@@H:7]([NH:15][C:16](=[O:37])[C@H:17]([CH2:31][C:32]1[N:36]=[CH:35][NH:34][CH:33]=1)[NH:18]C(OCC1C=CC(OC)=CC=1)=O)[CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)([CH3:3])[CH3:2].[ClH:40]>CO.[Pd]>[ClH:40].[ClH:40].[CH:1]([O:4][C:5](=[O:39])[CH:6]([OH:38])[C@@H:7]([NH:15][C:16](=[O:37])[C@H:17]([CH2:31][C:32]1[N:36]=[CH:35][NH:34][CH:33]=1)[NH2:18])[CH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 178491557HCID 178491557, compound

Product 1

HCID 178459632HCID 178459632, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

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. filtrationAfter filtration of the catalyst
  2. customthe filtrate was evaporated under reduced pressure

Sources & evidence

ORD record
ord-c2f713a8c0c148fb98f56854023175e0
Source dataset
uspto-grants-1989_09
Patent number
US04870183

Reaction notes

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