Piperidine → HCID 67031203, compound

HRID 456040Notes

Reaction equation

HRID 456040 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:30])[C:7]=1[CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17]C)=[C:13]([O:19][CH3:20])[C:12]=1[O:21][CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:10].N1CCCCC1>O>[Cl:30][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[CH2:8][C:9]([C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([O:19][CH3:20])[C:12]=1[O:21][CH2:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:10]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 24959219HCID 24959219, compound

Product 1

HCID 67031203HCID 67031203, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

2-(3,5-Dichloro-pyridin-4-yl)-1-(3,4-dimethoxy-2-phenethyloxy-phenyl)-ethanone obtained from example 112 (89.3 mg, 0.1 mmol) was treated with piperidine (0.8 mL) and water (0.32 mL). The yellow suspension was heated to 90° C. for 54 hours. The solvent was evaporated in vacuo. The crude mixture was treated with NH4Cl (sat., 1 mL) and the organic products were extracted with EtOAc (3×2 mL). The combined organic phases was dried over Na2SO4 and evaporated in vacuo. Purification by flash chromatography using a gradient of EtOAc in toluene as eluent provided 2-(3,5-dichloro-pyridin-4-yl)-1-(4-hydroxy-3-methoxy-2-phenethyloxy-phenyl)-ethanone as a white solid. Yield 8.6 mg (20%). 2-(3,5-Dichloro-pyridin-4-yl)-1-(4-hydroxy-3-methoxy-2-phenethyloxy-phenyl)-ethanone (5.5 mg, 0.013 mmol) was dissolved in DMSO (0.45 mL) and treated with K2CO3 (0.019 mL of a 1M aq. solution) followed by ethyliodide (0.019 mL of a 1M solution in DMSO). The reaction mixture was left at rt for 48 hours and purified by standard HPLC purification. 2-(3,5-Dichloro-pyridin-4-yl)-1-(4-ethoxy-3-methoxy-2-phenethyloxy-phenyl)-ethanone was obtained as a colourless solid. Yield 3.2 mg (36%).

Workup

  1. customThe solvent was evaporated in vacuo
  2. additionThe crude mixture was treated with NH4Cl (sat., 1 mL)
  3. extractionthe organic products were extracted with EtOAc (3×2 mL)
  4. dry with materialThe combined organic phases was dried over Na2SO4
  5. customevaporated in vacuo
  6. customPurification by flash chromatography

Sources & evidence

ORD record
ord-0f6f4bfb769b4b398bf755a6445bca1a
Source dataset
uspto-grants-2013_07
Patent number
US08497380B2

Reaction notes

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