4-Methylmorpholine → N-(tert-butoxycarbonyl)piperidine

HRID 1831838Notes

Reaction equation

HRID 1831838 reaction equation
CN1C[CH2:6][O:5]CC1.[CH3:8][CH:9]1[CH2:14]C(C)CN[CH2:10]1.[OH2:16].O[N:18]1[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26]C=2N=N1.Cl.CN(C)CCCN=C=NCC>CC(N(C)C)=O>[C:6]([N:18]1[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1)([O:5][C:9]([CH3:14])([CH3:10])[CH3:8])=[O:16]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 1182593,5-DimethylpiperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 7010304N-(tert-butoxycarbonyl)piperidineYield 96%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

Part A: To a solution of N-BOC-isoponic acid (4.0 g, 17.4 mmol) in dimethylacetamide (30 mL) were added N-methylmorpholine (Aldrich, 5.7 mL, 52.2 mmol), 3,5-dimethylpiperadine (70% cis, Aldrich, 3.5 mL, 26.1 mmol), N-hydroxybenzotriazole hydrate (Aldrich, 2.8 g, 20.9 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (Sigma, 5.0 g, 26.1 mmol). The mixture was stirred overnight (about 18 hours) at ambient temperature. To work up, the solvent was removed and the residue was taken up in ethyl acetate (300 mL) then washed with 5% KHSO4aq (1×100 ml), saturated K2CO3 aq (1×100 mL), and brine (1×100 mL). After drying over Na2SO4, the organic layer was filtered and concentrated to afford the BOC-piperidine as a tan oil that slowly crystallized (5.4 g, 96% yield). 1H NMR showed the desired compound existing as both the cis- and trans-isomers.

Workup

  1. customthe solvent was removed
  2. washthen washed with 5% KHSO4aq (1×100 ml), saturated K2CO3 aq (1×100 mL), and brine (1×100 mL)
  3. dry with materialAfter drying over Na2SO4
  4. filtrationthe organic layer was filtered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-8cc45bbe7cf24b0a838800839838e630
Source dataset
uspto-grants-2006_06
Patent number
US07067670B2

Reaction notes

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