4-Methylmorpholine → 1,1-Dimethylethyl 4-(3-methyl-1,2,4-oxadiazol-5-yl)-1-piperidinecarboxylate

HRID 1593005Notes

Reaction equation

HRID 1593005 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=N.O[N:45]=[C:46]([NH2:48])[CH3:47]>ClCCl.O1CCOCC1.O>[CH3:47][C:46]1[N:48]=[C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[O:16][N:45]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 30926N-HydroxyacetamidineHCID 757711-HydroxybenzotriazoleHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 21899179Dimethylaminopropyl carbodiimide hydrochloride

Product 1

HCID 210983601,1-Dimethylethyl 4-(3-methyl-1,2,4-oxadiazol-5-yl)-1-piperidinecarboxylateYield 98.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid (5.00 g, 21.83 mmol), 1-hydroxybenzotriazole (2.95 g, 21.83 mmol) and N-methylmorpholine (4.8 mL, 43.67 mmol) were dissolved in dichloromethane (100 mL), under argon, and (3-dimethylaminopropyl)carbodiimide hydrochloride (4.60 g, 24.0 mmol) and N′-hydroxyethanimidamide (1.62 g, 21.83 mmol) were added. The mixture was stirred at room temperature overnight then water (50 mL) was added and the mixture stirred for 30 minutes. The organics were separated, dried and the solvent evaporated to give a yellow oil which was redissolved in 1,4-dioxane (100 mL) and heated to 100° C. for 3 hours, cooled and the solvent evaporated to give crude tert-butyl 4-(3-methyl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate as a brown oil (5.74 g, 98.5%).

Workup

  1. stirringthe mixture stirred for 30 minutes
  2. customThe organics were separated
  3. customdried
  4. customthe solvent evaporated
  5. customto give a yellow oil which
  6. temperatureheated to 100° C. for 3 hours
  7. temperaturecooled
  8. customthe solvent evaporated

Sources & evidence

ORD record
ord-2af73ddbd3724644814829dff5443ebd
Source dataset
uspto-grants-2007_11
Patent number
US07294636B2

Reaction notes

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