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

HRID 1972032Notes

Reaction equation

HRID 1972032 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][C:26]=1[O:42][CH3:43])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>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:29]=[CH:30][C:25]([O:24][CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)=[C:26]([O:42][CH3:43])[CH:27]=3)[CH:36]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 866578214-(4-Benzyloxy-3-methoxy-phenyl)-3-butyl-6-chloro-pyridazine

Product 1

HCID 673747264-[5-(4-Benzyloxy-3-methoxy-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 (3.0 mmol, 604 mg) in THF (10 mL) at 0° C., NaH (60% dispersion in mineral oil, 4.0 mmol, 160 mg) was added and stirring continued for 10 min at room temperature, then 4-(4-benzyloxy-3-methoxy-phenyl)-3-butyl-6-chloro-pyridazine (2.0 mmol, 766 mg) was added. The resulting mixture was stirred at 50° C. for 1 hour, poured into ice-water and extracted with ethyl acetate. The organic layers were combined and concentrated under reduced pressure. The product was purified by column chromatography using 50% ethyl acetate in hexanes to give 4-[5-(4-benzyloxy-3-methoxy-phenyl)-6-butyl-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester, which was dissolved in dichloromethane (2.0 mL), added 4.0 M HCl in dioxane (2.0 mL) and stirred at room temperature for 1 hour. Solvents were evaporated in vacuo to give 4-(4-benzyloxy-3-methoxy-phenyl)-3-butyl-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (635 mg).

Workup

  1. stirringThe resulting mixture was stirred at 50° C. for 1 hour
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated under reduced pressure
  4. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-53bd927acd724d9fa721572296c23a33
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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