Water → 4-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 2168592Notes

Reaction equation

HRID 2168592 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[C:35](Cl)[N:34]=[N:33][C:32]=2[CH2:38][CH2:39][CH2:40][CH3:41])=[CH:27][CH:26]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:35]2[N:34]=[N:33][C:32]([CH2:38][CH2:39][CH2:40][CH3:41])=[C:31]([C:28]3[CH:27]=[CH:26][C:25]([O:24][CH2:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:30][CH:29]=3)[CH:36]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 713030894-(4-(Benzyloxy)phenyl)-3-butyl-6-chloropyridazine

Product 1

HCID 673733314-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (227 mg, 1.13 mmol) in THF (4.0 mL) at room temperature was added NaH (100 mg, 4.5 mmol). Stirring was continued for 10 min. To this solution was added 4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine (200 mg, 0.56 mmol) and the resulting mixture was stirred at 50-55° C. overnight. The reaction was poured into water and extracted with ethyl acetate. The organic layer was washed with water followed by brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by flash silica gel column chromatography using 30% ethyl acetate in hexanes to provide 4-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. stirringthe resulting mixture was stirred at 50-55° C. overnight
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-a682beaea9c0494289bb64ee1c080b38
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

Loading…