Sodium ethoxide → Bis(1,1-Dimethylethyl) 2-[3-(ethyloxy)-3-oxopropanoyl]-1,4-piperazinedicarboxylate

HRID 1427151Notes

Reaction equation

HRID 1427151 reaction equation
[CH3:1][C:2]1(C)OC(=O)[C:5](=[C:9]([OH:30])[CH:10]2[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][CH2:12][N:11]2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:4](=[O:31])[O:3]1.[O-]CC.[Na+]>C(O)C>[CH2:2]([O:3][C:4](=[O:31])[CH2:5][C:9]([CH:10]1[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13][CH2:12][N:11]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:30])[CH3:1]

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 70568232Bis(1,1-Dimethylethyl) 2-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(hydroxy)methyl]-1,4-piperazinedicarboxylate2×

Product 1

HCID 70559668Bis(1,1-Dimethylethyl) 2-[3-(ethyloxy)-3-oxopropanoyl]-1,4-piperazinedicarboxylateYield 46.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of bis(1,1-dimethylethyl) 2-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)(hydroxy)methyl]-1,4-piperazinedicarboxylate (may be prepared as described in Intermediate 2; 8.32 g) in ethanol (250 mL) under argon, cooled to 0° C., was added dropwise a 21% weight solution of sodium ethoxide (118 mL). After completion of addition, the reaction was heated to reflux for 18 hours. The reaction mixture was evaporated and the residue partitioned between 2× ethyl acetate and water. The combined organic phases were washed with brine, dried through a hydrophobic frit, then evaporated to an orange oil. An attempt was made to dissolve in DCM for purification but a solid formed. This was evaporated and then triturated in ether. The resulting cream solid was collected by filtration, but was an impurity. The liquors were evaporated and then purified by silica column (SP4-40M) eluting with 0-40% ethyl acetate in iso-hexane over 12 CV. The clean fractions were combined and evaporated to give the title compound as a yellow oil (3.40 g).

Workup

  1. additionAfter completion of addition
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 18 hours
  4. customThe reaction mixture was evaporated
  5. customthe residue partitioned between 2× ethyl acetate and water
  6. washThe combined organic phases were washed with brine
  7. customdried through a hydrophobic frit
  8. customevaporated to an orange oil
  9. dissolutionto dissolve in DCM for purification
  10. customa solid formed
  11. customThis was evaporated
  12. customtriturated in ether
  13. filtrationThe resulting cream solid was collected by filtration
  14. customThe liquors were evaporated
  15. custompurified by silica column (SP4-40M)
  16. washeluting with 0-40% ethyl acetate in iso-hexane over 12 CV
  17. customevaporated

Sources & evidence

ORD record
ord-4e08ad1a7dfd418db4e7da8d964e6dca
Source dataset
uspto-grants-2015_01
Patent number
US08933132B2

Reaction notes

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