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

HRID 353113노트

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HRID 353113 반응식
[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

참가 물질

10

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-3cb8feccb399418db6d8b5d787e68813
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06750231B2

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