Ammonium Chloride → 3,4-Dimethyl-1-(3-tetrahydro-3-furanylpropyl)-4-(3-(1H-1,2,3-triazol-4-yl)phenyl)piperidine

HRID 353113Notes

Reaction equation

HRID 353113 reaction equation
[CH3:1][CH:2]1[C:7]([CH3:19])([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[N:15]=[N:16][NH:17][CH:18]=3)[CH:9]=2)[CH2:6][CH2:5][NH:4][CH2:3]1.[O:20]1[CH2:24][CH2:23][CH:22]([CH2:25][CH2:26][C:27](O)=O)[CH2:21]1.Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+].[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl-].[NH4+]>CN(C)C=O.O1CCCC1>[CH3:1][CH:2]1[C:7]([CH3:19])([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]3[N:15]=[N:16][NH:17][CH:18]=3)[CH:9]=2)[CH2:6][CH2:5][N:4]([CH2:27][CH2:26][CH2:25][CH:22]2[CH2:23][CH2:24][O:20][CH2:21]2)[CH2:3]1

Participants

10

Reactant 7

HCID 25517Ammonium ChlorideHCID 2840903-(Oxolan-3-yl)propanoic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 21226445Aluminium lithium hydrideHCID 178430465HCID 178430465, compound

Product 1

HCID 1784304953,4-Dimethyl-1-(3-tetrahydro-3-furanylpropyl)-4-(3-(1H-1,2,3-triazol-4-yl)phenyl)piperidineYield 26%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3,4-dimethyl-4-(3-(1H-1,2,3-triazol-4-yl)phenyl)piperidine (Preparation 44, 45 mg, 0.18 mmol) in N,N-dimethylformamide (5 mL) was added 3-(tetrahydro-3-furanyl)propionic acid (Preparation 47, 28 mg, 0.19 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (44 mg, 0.23 mmol) and 1-hydroxybenzotriazole hydrate (24 mg, 0.18 mmol). The resultant mixture was heated to 80° C. and stirred overnight. The reaction mixture was cooled, poured onto saturated aqueous sodium hydrogencarbonate solution (100 mL) and extracted with ethyl acetate (3×20 mL). The combined organics were dried over MgSO4 and concentrated in vacuo to give an off-white gum. The product was dissolved in tetrahydrofuran (2 mL) and cooled to 0° C. The solution was treated dropwise with lithium aluminium hydride (1.0 M solution in THF, 0.35 mL, 0.35 mmol). The reaction was allowed to warm to room temperature and stirred overnight. The reaction mixture was treated with saturated ammonium chloride solution and the product extracted with ethyl acetate (3×10 mL). The combined organics were dried over Na2SO4 and the solvent removed in vacuo to give a white gum. The crude product was purified by reverse-phase high performance liquid chromatography (condition 1) to give the title compound as a clear oil (17 mg, 26%).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organics were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customto give an off-white gum
  6. temperatureto warm to room temperature
  7. stirringstirred overnight
  8. extractionthe product extracted with ethyl acetate (3×10 mL)
  9. dry with materialThe combined organics were dried over Na2SO4
  10. customthe solvent removed in vacuo
  11. customto give a white gum
  12. customThe crude product was purified by reverse-phase high performance liquid chromatography (condition 1)

Sources & evidence

ORD record
ord-3cb8feccb399418db6d8b5d787e68813
Source dataset
uspto-grants-2004_06
Patent number
US06750231B2

Reaction notes

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