Triethylamine → 1-Piperidinecarboxylic acid, 4-amino-4-(phenylmethyl)-, 1,1-dimethylethyl ester

HRID 645504Notes

Reaction equation

HRID 645504 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)(C(O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:26](CC)CC.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1>O1CCOCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([NH2:26])([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 121510204-Benzyl-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid

Product 1

HCID 206647191-Piperidinecarboxylic acid, 4-amino-4-(phenylmethyl)-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 4-benzyl-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (0.65 mmol) in 1,4-dioxane (2 mL) are added Et3N (0.71 mmol) and DPPA (0.71 mmol) at room temperature. After warming to 100° C. and stirring for 2 h, the reaction mixture is diluted with AcOEt. The organic layer is washed with sat. aq. NaHCO3 and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue is dissolved in THF (4 mL) and 6N aq. NaOH (0.22 mL) is added at room temperature. After stirring for 4 h, the reaction mixture is diluted with CH2Cl2, washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue is purified by silica gel column chromatography to give the title compound; 1H NMR (CDCl3), δ: 1.18 (2H, bs), 1.28-1.37 (2H, m), 1.46 (9H, s), 1.51-1.64 (2H, m), 2.66 (2H, s), 3.20 (2H, dd), 3.74 (2H, bd), 7.13-7.19 (2H, m), 7.21-7.34 (3H, m).

Workup

  1. washThe organic layer is washed with sat. aq. NaHCO3 and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue is dissolved in THF (4 mL)
  6. addition6N aq. NaOH (0.22 mL) is added at room temperature
  7. stirringAfter stirring for 4 h
  8. additionthe reaction mixture is diluted with CH2Cl2
  9. washwashed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-79df5b72c068414693fb49758c16de70
Source dataset
uspto-grants-2010_04
Patent number
US07704996B2

Reaction notes

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