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

HRID 1186217Notes

Reaction equation

HRID 1186217 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:27]([O:31][C:32]([O:34]N=C(C1C=CC=CC=1)C#N)=O)([CH3:30])([CH3:29])[CH3:28]>CO>[CH3:25][O:24][C:22]([CH2:21][CH:9]1[NH:8][CH2:13][CH2:12][N:11]([C:32]([O:31][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:34])[CH2:10]1)=[O:23]

Participants

5

Reactant 3

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

Product 1

HCID 2756816Methyl 4-Boc-piperazine-2-acetate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The product of example 22A (9.78 g, 28.9 mmol) was combined with 20% Pd(OH)2—C (wet, 1.96 g) in methanol (100 mL) and 12 M aqueous HCl (2.9 mL, 35 mmol). The mixture was stirred under hydrogen (30 psi) at room temperature for 22 hours, then filtered and concentrated under vacuum. The residue was combined with 20% aqueous K2CO3 (40 mL) and ethyl acetate (50 mL), and the mixture stirred with ice-cooling as 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (Aldrich, 7.12 g, 28.9 mmol) was added gradually over 5 minutes. The mixture was stirred with ice cooling for 1 hour, then it was allowed to warm to room temperature for 2 hours. The mixture was extracted with ethyl acetate (2×100 mL) and the combined ethyl acetate washes were extracted with 10% aqueous HCl (40 mL). The aqueous layer was washed with ethyl acetate (30 mL), then made basic (pH˜9) by gradual addition of solid K2CO3 (11.8 g). Ethyl acetate (80 mL) was added, and the mixture was stirred at room temperature for 30 minutes. The aqueous phase was separated, and the organic phase was washed with brine (50 mL), dried (MgSO4) and concentrated under vacuum to leave the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.46 (s, 9H), 2.31-2.49 (m, 2H), 2.50-2.68 (m, 1H), 2.72-2.81 (m, 1H), 2.82-2.98 (m, 2H), 2.98-3.09 (m, 1H), 3.70 (s, 3H), 3.90 (d, J=9.9 Hz, 2H); MS (DCI) m/z 259 (M+H)+.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated under vacuum
  3. stirringthe mixture stirred with ice-
  4. additionwas added gradually over 5 minutes
  5. stirringThe mixture was stirred with ice cooling for 1 hour
  6. temperatureto warm to room temperature for 2 hours
  7. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
  8. extractionthe combined ethyl acetate washes were extracted with 10% aqueous HCl (40 mL)
  9. washThe aqueous layer was washed with ethyl acetate (30 mL)
  10. additionby gradual addition of solid K2CO3 (11.8 g)
  11. additionEthyl acetate (80 mL) was added
  12. stirringthe mixture was stirred at room temperature for 30 minutes
  13. customThe aqueous phase was separated
  14. washthe organic phase was washed with brine (50 mL)
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-27ddfb589614447f8a4bfa8b8d0f698f
Source dataset
uspto-grants-2014_03
Patent number
US08673896B2

Reaction notes

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