Hydrochloric Acid → HCID 66594459, compound

HRID 1091384Notes

Reaction equation

HRID 1091384 reaction equation
[ClH:1].[CH3:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([C@H:14]3[CH2:19][N:18](C([O-])=O)[CH2:17][CH2:16][N:15]3C([O-])=O)=[CH:10][CH:9]=2)[N:4]=1>C(OCC)(=O)C.CO>[ClH:1].[ClH:1].[CH3:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([C@H:14]3[CH2:19][NH:18][CH2:17][CH2:16][NH:15]3)=[CH:10][CH:9]=2)[N:4]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86634558HCID 86634558, compound

Product 1

HCID 66594459HCID 66594459, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Hydroxylamine hydrochloride (1.3 g, 20.2 mmol) and sodium carbonate (3.4 g, 32.1 mmol) were added to a solution of di-tert-butyl (2S)-2-(4-cyanophenyl)piperazine-1,4-dicarboxylate (2.5 g, 6.45 mmol) in ethanol (15 ml) and water (15 ml) at room temperature and the solution was stirred at 80° C. for 2 hours. The mixture was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. Triethyl orthoacetate (10.5 g, 64.7 mmol) and p-toluenesulfonic acid monohydrate (0.12 g, 0.63 mmol) were added to the solution of the residue in toluene (25 ml) and the solution was stirred at 90° C. for 2 hours. The mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 10-20% ethyl acetate in hexane to furnish (2S)-2-(4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenyl)piperazine-1,4-dicarboxylate (1.0 g, 35%) as a colorless oil. Hydrogen chloride in ethyl acetate (4N) was added to a solution of (2S)-2-(4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenyl)piperazine-1,4-dicarboxylate (1.0 g, 2.25 mmol) in methanol and the mixture stirred at room temperature for one hour. The solvent was evaporated under reduced pressure to give a white solid, which was washed with ethyl acetate to afford (2S)-2-(4-(5-Methyl-[1,2,4]oxadiazol-3-yl)phenyl)piperazine dihydrochloride (0.64 g, 100%) as white crystals.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customto give a white solid, which
  3. washwas washed with ethyl acetate

Sources & evidence

ORD record
ord-fa55a333480b4c9db380552f6ffb2767
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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