Hydrochloric Acid → Methyl 4-Boc-piperazine-2-acetate

HRID 352638Notes

Reaction equation

HRID 352638 reaction equation
C([N:8]1[CH2:13][CH2:12][N:11](CC2C=CC=CC=2)[CH2:10][CH:9]1[CH2:21][C:22]([O:24][CH3:25])=[O:23])C1C=CC=CC=1.Cl.C([O-])([O-])=O.[K+].[K+].[CH3:33][C:34]([O:37][C:38]([O:40]N=C(C1C=CC=CC=1)C#N)=O)([CH3:36])[CH3:35]>[Pd].CO>[C:38]([N:11]1[CH2:12][CH2:13][NH:8][CH:9]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[CH2:10]1)([O:37][C:34]([CH3:33])([CH3:35])[CH3:36])=[O:40]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 938652-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrileHCID 22710010Methyl 2-(1,4-dibenzylpiperazin-2-yl)acetate

Product 1

HCID 2756816Methyl 4-Boc-piperazine-2-acetateYield 76.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

The 13.7 g (40 mmol) of methyl 1,4-dibenzylpiperazine-2-acetate, 150 mL of MeOH, 50 mL of 1 N HCl (aqueous) and 3 g of 10% Pd/C were combined and hydrogenated with H2 (50 psi) for 24 hours. The reaction was filtered, the filtrate was concentrated in vacuo to remove most of the MeOH, and the residue was made basic with K2CO3 to pH=9-10, and 9.8 g (40 mmol) of BOC-ON was added slowly at 0° C. The reaction was stirred at 0° for 1 hour, allowed to warm up to room temperature, stirred for 2 hours, and extracted with ethyl acetate (2×200 mL). The combined extracts were treated with 50 mL of 10% HCl (aqueous). The aqueous layer was washed with ethyl acetate, basified with K2CO3 and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo to give 7.89 g of methyl 4-Boc-piperazine-2-acetate; 1H NMR (CDCl3) δ1.4 (s, 9), 2.31 (dd, 1), 2.37 (dd, 1), 2.55 (b, 1), 2.69-3.02 (m, 4), 3.75 (s, 3), 3.88 (b, 2).

Workup

  1. filtrationThe reaction was filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. customto remove most of the MeOH
  4. additionwas added slowly at 0° C
  5. stirringstirred for 2 hours
  6. extractionextracted with ethyl acetate (2×200 mL)
  7. additionThe combined extracts were treated with 50 mL of 10% HCl (aqueous)
  8. washThe aqueous layer was washed with ethyl acetate
  9. extractionextracted three times with ethyl acetate
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8f01d00ff6df43a2bbeac16e7805914d
Source dataset
uspto-grants-2004_06
Patent number
US06747031B2

Reaction notes

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