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

HRID 1971902

Reaction equation

HRID 1971902 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].CC(C)([O-])C.[K+].[CH2:21]([C:25]1[N:26]=[N:27][C:28](Cl)=[CH:29][C:30]=1[C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)=[CH:33][CH:32]=1)[CH2:22][CH2:23][CH3:24].O>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:28]2[N:27]=[N:26][C:25]([CH2:21][CH2:22][CH2:23][CH3:24])=[C:30]([C:31]3[CH:32]=[CH:33][C:34]([O:37][CH:38]4[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]4)=[CH:35][CH:36]=3)[CH:29]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 866577793-Butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine

Product 1

HCID 673746634-[6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (94.2 mmol, 18.97 g) in THF (100 mL) at room temperature was added potassium tert-butoxide (87.0 mmol, 9.76 g) and continued stirring for 15 min. The reaction mixture was cooled to 0° C. using an ice bath. To this was added a solution of 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine (72.5 mmol, 25.0 g) in THF (100 mL). The reaction mixture was allowed to slowly attain room temperature while stirring overnight. The reaction was poured into a mixture of water (300 mL) and ethyl acetate (300 mL). The mixture was shaken and separated. The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layer was washed with brine (50 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on 330 g SiO2 cartridge using an ethyl acetate/hexanes gradient to provide 4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-pieridine-1-carboxylic acid tert-butyl ester.

Workup

  1. customwas allowed to slowly attain room temperature
  2. stirringwhile stirring overnight
  3. stirringThe mixture was shaken
  4. customseparated
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  6. washThe combined organic layer was washed with brine (50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on 330 g SiO2 cartridge

Sources & evidence

ORD record
ord-93451efe296c425db2f02d550905e984
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Linked notes

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