Hydrochloric Acid → ethyl (2E)-3-{5-[(3R)-3-piperidinylamino]-2-pyrazinyl)acrylate dihydrochloride

HRID 226368Notes

Reaction equation

HRID 226368 reaction equation
[CH2:1]([O:3][C:4](=[O:27])/[CH:5]=[CH:6]/[C:7]1[N:8]=[CH:9][C:10]([NH:13][C@@H:14]2[CH2:19][CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15]2)=[N:11][CH:12]=1)[CH3:2].[ClH:28]>O1CCOCC1.CO.C(OCC)(=O)C.O>[ClH:28].[ClH:28].[NH:16]1[CH2:17][CH2:18][CH2:19][C@@H:14]([NH:13][C:10]2[N:11]=[CH:12][C:7](/[CH:6]=[CH:5]/[C:4]([O:3][CH2:1][CH3:2])=[O:27])=[N:8][CH:9]=2)[CH2:15]1

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 86603674tert-butyl (3R)-3-({5-[(1E)-3-ethoxy-3-oxo-1-propen-1-yl]-2-pyrazinyl}amino)-1-piperidinecarboxylate

Product 1

HCID 86603669ethyl (2E)-3-{5-[(3R)-3-piperidinylamino]-2-pyrazinyl)acrylate dihydrochloride

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl (3R)-3-({5-[(1E)-3-ethoxy-3-oxo-1-propen-1-yl]-2-pyrazinyl}amino)-1-piperidinecarboxylate (6.26 g) in a mixture of 1,4-dioxane (25 mL) and MeOH (5 mL) was added 4N hydrogen chloride solution in ethyl acetate (30 mL) in water bath. The mixture was stirred at same temperature for 3 hrs. After evaporation of solvent, the residue was triturated with isopropylether to give ethyl (2E)-3-{5-[(3R)-3-piperidinylamino]-2-pyrazinyl}acrylate dihydrochloride (5.8 g) as an amorphous powder. 1H-NMR (300 MHz, DMSO-d6) δ 1.25 (3H, t, J=7 Hz), 1.46-1.65 (1H, m), 1.65-1.85 (1H, m), 1.85-2.06 (3H, m), 2.66-3.00 (2H, m), 3.05-3.25 (1H, m), 3.25-3.41 (1H, m), 4.18 (2H, q, J=7 Hz), 6.54 (1H, d, J=15 Hz), 7.57 (1H, d, J=15 Hz), 7.95-8.19 (2H, m), 8.28 (1H, s), 9.14 (2H, br peak)

Workup

  1. customAfter evaporation of solvent
  2. customthe residue was triturated with isopropylether

Sources & evidence

ORD record
ord-51f1192102694e3881d0f9062e2c0c85
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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