Formaldehyde → 4-(4-Benzyloxy-phenyl)-3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazine

HRID 401866Notes

Reaction equation

HRID 401866 reaction equation
Cl.Cl.[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[C:21]([O:23][CH:24]3[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]3)[N:20]=[N:19][C:18]=2[CH2:30][CH2:31][CH2:32][CH3:33])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C=O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[C:21]([O:23][CH:24]3[CH2:29][CH2:28][N:27]([CH3:36])[CH2:26][CH2:25]3)[N:20]=[N:19][C:18]=2[CH2:30][CH2:31][CH2:32][CH3:33])=[CH:13][CH:12]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 673745154-(4-Benzyloxy-phenyl)-3-butyl-6-(piperidin-4-yloxy)-pyridazine dihydrochloride

Product 1

HCID 533718084-(4-Benzyloxy-phenyl)-3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A stirred suspension of 4-(4-Benzyloxy-phenyl)-3-butyl-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (0.34 mmol, 170 mg) and paraformaldehyde (6.1 mmol, 550 mg) in DCM was stirred for 20 min then sodiumtriacetoxyborohydride (6.1 mmol, 1.2 g) was added. Stirring was continued overnight. The solvent was evaporated and saturated NaHCO3 solution was added to the residue. The mixture was extracted with ethyl acetate. The organic layer was washed with water, brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The resultant product was purified by flash silica gel column chromatography using 5% methanolic solution of ammonia (2.0 M ammonia in methanol) in DCM to provide 4-(4-benzyloxy-phenyl)-3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazine.

Workup

  1. stirringStirring
  2. waitwas continued overnight
  3. customThe solvent was evaporated
  4. additionsaturated NaHCO3 solution was added to the residue
  5. extractionThe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe resultant product was purified by flash silica gel column chromatography

Sources & evidence

ORD record
ord-6693c8e5bc6c419b9799cf651df7222c
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

Loading…