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

HRID 401880Notes

Reaction equation

HRID 401880 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH:35]=[C:34](Cl)[N:33]=[N:32][C:31]=2[CH2:37][CH2:38][CH2:39][CH3:40])=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][O:13][C:34]2[N:33]=[N:32][C:31]([CH2:37][CH2:38][CH2:39][CH3:40])=[C:30]([C:27]3[CH:26]=[CH:25][C:24]([O:23][CH2:16][C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)=[CH:29][CH:28]=3)[CH:35]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 10583745tert-Butyl 3-(hydroxymethyl)azetidine-1-carboxylateHCID 713030894-(4-(Benzyloxy)phenyl)-3-butyl-6-chloropyridazine

Product 1

HCID 673734983-[5-(4-Benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-azetidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-hydroxymethyl-azetidine-1-carboxylic acid tert-butyl ester (1.5 mmol, 281 mg) in THF (4.0 mL) at 0° C., NaH (60% dispersion in mineral oil, 1.5 mmol, 60 mg) was added and stirring continued for 10 min at room temperature, then 4-(4-benzyloxy-phenyl)-3-butyl-6-chloro-pyridazine (Example 1, 1.0 mmol, 352 mg) was added. The resulting mixture was stirred at 50° C. for 1 hour, poured into 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 3-[5-(4-benzyloxy-phenyl)-6-butyl-pyridazin-3-yloxymethyl]-azetidine-1-carboxylic acid tert-butyl ester, which was dissolved in dichloromethane (1.0 mL), added 4.0 M HCl in dioxane (1.0 mL) and stirred at room temperature for 1 hour. Solvents were evaporated to give 6-(azetidin-3-ylmethoxy)-4-(4-benzyloxy-phenyl)-3-butyl-pyridazine dihydrochloride.

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-ac13ad5a382948b7b628fb2efad090fb
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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