tert-Butyl 4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-3-oxopiperazine-1-carboxylate → 1-[2-(1,3-Dihydro-4-methyl-1-oxo-5-isobenzofuranyl)ethyl]-2-piperazinone

HRID 1466064Notes

Reaction equation

HRID 1466064 reaction equation
O[CH:2]([C:18]1[CH:27]=[CH:26][C:21]2[C:22](=[O:25])[O:23][CH2:24][C:20]=2[C:19]=1[CH3:28])[CH2:3][N:4]1[CH2:9][CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6][C:5]1=[O:17]>CO.[OH-].[OH-].[Pd+2]>[CH3:28][C:19]1[C:20]2[CH2:24][O:23][C:22](=[O:25])[C:21]=2[CH:26]=[CH:27][C:18]=1[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][C:5]1=[O:17]

Participants

4

Reactant 1

HCID 89526106tert-Butyl 4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-3-oxopiperazine-1-carboxylate

Product 1

HCID 895334771-[2-(1,3-Dihydro-4-methyl-1-oxo-5-isobenzofuranyl)ethyl]-2-piperazinone

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

A solution of tert-butyl 4-[2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-3-oxopiperazine-1-carboxylate (160 mg, 0.41 mmol) in 20 mL of MeOH was treated with Pd(OH)2 (120 mg, 0.21 mmol) was stirred under 40 psi atmosphere of H2 at 60 C. After 18 hrs the solution was filtered through a pad of celite which was subsequently washed with EtOAc. The filtrate was concentrated and the residue was then redissolved in 2 mL of DCM was treated with 4 mL of 4N HCl in dioxane at room temperature. After 2 hours excess solvent was removed and the residue partitioned between 3 mL of 1N NaOH and 10 mL of 10% IPA/Chloroform. The organic layer was collected, dried over magnesium sulfate, filtered and concentrated to give the title product. The free amine was used without further purification. 1H NMR (500 MHz; CDCl3): 7.82 (m, 2H), 5.40 (dd, J=2.3, 8.0 Hz, 1H), 5.27 (s, 1H), 3.74-3.70 (m, 1H), 3.61 (s, 2H), 3.45-3.41 (m, 1H), 3.38-3.34 (m, 1H), 3.26-3.22 (m, 1H), 3.04-3.01 (m, 2H), 2.06 (s, 3H).

Workup

  1. filtrationAfter 18 hrs the solution was filtered through a pad of celite which
  2. washwas subsequently washed with EtOAc
  3. concentrationThe filtrate was concentrated
  4. dissolutionthe residue was then redissolved in 2 mL of DCM
  5. additionwas treated with 4 mL of 4N HCl in dioxane at room temperature
  6. customAfter 2 hours excess solvent was removed
  7. customthe residue partitioned between 3 mL of 1N NaOH and 10 mL of 10% IPA/Chloroform
  8. customThe organic layer was collected
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-7262a0518460444987052e0e2d993803
Source dataset
uspto-grants-2015_04
Patent number
US08999990B2

Reaction notes

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