Methylamine → Benzyl 4-((tert-butoxycarbonyl)(methyl)amino)piperidine-1-carboxylate

HRID 2354070Notes

Reaction equation

HRID 2354070 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:18][NH2:19].[C:20]([O:24][C:25]([O:27]C(OC(C)(C)C)=O)=O)([CH3:23])([CH3:22])[CH3:21]>O1CCOCC1.CCOCC>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:19]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:27])[CH3:18])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6329MethylamineHCID 90495Di-tert-butyl dicarbonateHCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 20782499Benzyl 4-((tert-butoxycarbonyl)(methyl)amino)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of commercially available 4-oxo-piperidine-1-carboxylic acid benzyl ester (4.67 g, 20 mmol) and methylamine (8 M in EtOH, 12.5 mL, 100 mmol) in dioxane (total volume of 100 mL) is stirred at r.t. for 15 min. NaBHAc3 (6.4 g, 30 mmol) is added and the mixture is stirred for 15 h. The mixture is quenched with 1 M aq. NaOH (30 mL) and stirred at r.t. for 30 min. The mixture is diluted with water (50 mL) and extracted with CH2Cl2 (3×75 mL). The organic extracts are dried (Na2SO4), filtered and evaporated. The residue is dissolved in ether (200 mL) and TEA (1.4 mL, 10 mmol) and, subsequently, a solution of di-tert.butyl-dicarbonat (3.82 g, 17.5 mmol) in ether (10 mL) are added. The mixture is stirred at r.t. for 15 h and quenched with 1 M aq. NaOH (30 mL). The phases are separated and the organic phase is washed with 1 M aq. NaOH (30 mL), 1 M aq. KHSO4 (2×30 mL) and sat. aq. NaCl (30 mL). The organic phase is dried (Na2SO4), filtered and evaporated to provide the title compound.

Workup

  1. additionNaBHAc3 (6.4 g, 30 mmol) is added
  2. stirringthe mixture is stirred for 15 h
  3. customThe mixture is quenched with 1 M aq. NaOH (30 mL)
  4. stirringstirred at r.t. for 30 min
  5. additionThe mixture is diluted with water (50 mL)
  6. extractionextracted with CH2Cl2 (3×75 mL)
  7. dry with materialThe organic extracts are dried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe residue is dissolved in ether (200 mL)
  11. stirringThe mixture is stirred at r.t. for 15 h
  12. customquenched with 1 M aq. NaOH (30 mL)
  13. customThe phases are separated
  14. washthe organic phase is washed with 1 M aq. NaOH (30 mL), 1 M aq. KHSO4 (2×30 mL) and sat. aq. NaCl (30 mL)
  15. dry with materialThe organic phase is dried (Na2SO4)
  16. filtrationfiltered
  17. customevaporated

Sources & evidence

ORD record
ord-94c9b226da5b4b5f983ffeb77fd3412a
Source dataset
uspto-grants-2010_07
Patent number
US07750161B2

Reaction notes

Loading…