Toluene → HCID 59731914, compound

HRID 132348Notes

Reaction equation

HRID 132348 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[C:15](Cl)(Cl)=[O:16].[C:19]1(C)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>ClCCl.C(=O)(O)[O-].[Na+].C(OCC)(=O)C>[CH2:11]([O:10][C:15](=[O:16])[CH2:4][N:5]([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:8](=[O:9])[NH:1][CH:2]1[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]1)[CH3:12]

Participants

7

Reactant 3

HCID 1140TolueneHCID 6371PhosgeneHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 59731914HCID 59731914, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

4-Amino-1-N-Boc-piperidine (760 mg, 3.79 mmol) was dissolved in a mixture of dichloromethane (40 mL) and aqueous sodium bicarbonate (30 mL). A solution of 20% phosgene in toluene (10 mL, 18.9 mmol) was added to the mixture with vigorous stirring. Reaction stirred vigorously at room temperature for 40 minutes. Reaction layers were partitioned. Organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo. Residue was dissolved in toluene (30 mL). N-Phenylglycine ethyl ester was added to the mixture. Reaction was heated at reflux for 15 hours. Mixture was cooled to room temperature and diluted with ethyl acetate (50 mL). Mixture was washed successively with 1N hydrochloric acid (3×50 mL) and brine (30 mL). Organic layer was dried (magnesium sulfate), filtered and concentrated in vacuo. Silica gel chromatography afforded the title compound as pale yellow solid in 63% yield. 1H NMR (300 MHz, CDCl3): δ=7.47-7.26 (m, 5H), 4.30 (s, 1H), 4.16 (q, J=7.32, 2H), 3.88 (d, J=12.81, 2H), 3.81-3.69 (m , 1H), 2.80-2.70 (m, 2H), 1.83 (dd, J1=12.62, J2=3.11, 2H), 1.38 (s, 9H), 1.23 (t, J=7.14, 3H), 1.19-1.03 (m, 2H).

Workup

  1. customReaction
  2. customReaction layers
  3. customwere partitioned
  4. dry with materialOrganic layer was dried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionResidue was dissolved in toluene (30 mL)
  8. additionN-Phenylglycine ethyl ester was added to the mixture
  9. customReaction
  10. temperaturewas heated
  11. temperatureat reflux for 15 hours
  12. temperatureMixture was cooled to room temperature
  13. washMixture was washed successively with 1N hydrochloric acid (3×50 mL) and brine (30 mL)
  14. dry with materialOrganic layer was dried (magnesium sulfate)
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6d8782e5fbe246fa951e8b118f88a8e3
Source dataset
uspto-grants-2008_06
Patent number
US07384931B2

Reaction notes

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