Butyn-2-one → Bis(1,1-Dimethylethyl) 2-{3-[(ethyloxy)carbonyl]-6-methyl-2-pyridinyl}-1,4-piperazinedicarboxylate

HRID 1427153Notes

Reaction equation

HRID 1427153 reaction equation
[NH2:1]/[C:2](/[CH:9]1[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12][CH2:11][N:10]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[CH:3]\[C:4]([O:6][CH2:7][CH3:8])=[O:5].[CH3:29][C:30](=O)[C:31]#[CH:32]>C(O)C>[CH2:7]([O:6][C:4]([C:3]1[C:2]([CH:9]2[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:12][CH2:11][N:10]2[C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])=[N:1][C:31]([CH3:32])=[CH:30][CH:29]=1)=[O:5])[CH3:8]

Participants

4

Reactant 2

HCID 15018Butyn-2-oneHCID 70556570Bis(1,1-Dimethylethyl) 2-[(1Z)-1-amino-3-(ethyloxy)-3-oxo-1-propen-1-yl]-1,4-piperazinedicarboxylate2×

Product 1

HCID 68176488Bis(1,1-Dimethylethyl) 2-{3-[(ethyloxy)carbonyl]-6-methyl-2-pyridinyl}-1,4-piperazinedicarboxylateYield 59.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of bis(1,1-dimethylethyl) 2-[(1Z)-1-amino-3-(ethyloxy)-3-oxo-1-propen-1-yl]-1,4-piperazinedicarboxylate (may be prepared as described in Intermediate 4; 7.4 g) in ethanol (300 mL), was added 3-butyn-2-one (3.15 g) and the reaction was heated to reflux for 20 hours. The reaction mixture was evaporated and then partitioned between 2× EtOAc and water. The combined organic phases were washed with brine, dried through a hydrophobic frit, and then evaporated to a brown oil (8.54 g), which was purified by silica column (SP4-40M) eluting with 0-40% ethyl acetate in isohexane over 12CV. The clean fractions were combined and evaporated to give the title compound as a yellow oil (4.96 g).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux for 20 hours
  3. customThe reaction mixture was evaporated
  4. custompartitioned between 2× EtOAc and water
  5. washThe combined organic phases were washed with brine
  6. customdried through a hydrophobic frit
  7. customevaporated to a brown oil (8.54 g), which
  8. customwas purified by silica column (SP4-40M)
  9. washeluting with 0-40% ethyl acetate in isohexane over 12CV
  10. customevaporated

Sources & evidence

ORD record
ord-6c7b0824073c43a694beb0294dff5d5c
Source dataset
uspto-grants-2015_01
Patent number
US08933132B2

Reaction notes

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