Formaldehyde → HCID 18693270, compound

HRID 1870773Notes

Reaction equation

HRID 1870773 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:20]CC(C)=C)=[C:6]([CH:19]=1)[CH2:7][N:8]([C:11]1[N:16]=[N:15][C:14](C#N)=[CH:13][CH:12]=1)[CH2:9][CH3:10].[CH2:25]=[O:26].F[C:28]1C=C[C:31]([OH:34])=[CH:30][CH:29]=1.C(O)(C(F)(F)[F:38])=O>>[F:38][C:2]1[CH:3]=[CH:4][C:5]([OH:20])=[C:6]([CH:19]=1)[CH2:7][N:8]([C:11]1[N:16]=[N:15][C:14]([C:25]([O:34][CH2:31][CH2:30][CH2:29][CH3:28])=[O:26])=[CH:13][CH:12]=1)[CH2:9][CH3:10]

Participants

5

Reactant 4

HCID 712FormaldehydeHCID 6422Trifluoroacetic acidHCID 97324-FluorophenolHCID 18693219HCID 18693219, compound

Product 1

HCID 18693270HCID 18693270, compound

Conditions

Temperature
55 °C

Procedure

A mixture of butyl 6-ethylaminopyridazine 3-carboxylate (described in reference example 13)(10.0 g, 44.8 mmol) and para-formaldehyde (1.7 g, 56.6 mmol) in TFA (100 ml was stirred at 50-60° C. for 1 hour until a clear solution formed. The solution was cooled to ambient temperature and treated with 4-fluorophenol (5.6 g, 50 0 mmol), stirred for 16 hours and evaporated at reduced pressure. The residue was partitioned between ice/water (200 g) and dichloromethane (200 ml), the organic layer washed with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulphate and evaporated to give a yellow gum. Chromatography on silica, eluting with 10% ether in dichloromethane, gave a solid which crystallised from ether to give butyl 6-[N-(5-fluoro-2-hydroxybenzyl)-N-ethylamino]pyridazine-3-carboxylate as pale pink needles (2.2 g).

Workup

  1. customformed
  2. temperatureThe solution was cooled to ambient temperature
  3. stirringstirred for 16 hours
  4. customevaporated at reduced pressure
  5. customThe residue was partitioned between ice/water (200 g) and dichloromethane (200 ml)
  6. washthe organic layer washed with saturated sodium bicarbonate solution
  7. dry with materialdried over anhydrous magnesium sulphate
  8. customevaporated
  9. customto give a yellow gum
  10. washChromatography on silica, eluting with 10% ether in dichloromethane
  11. customgave a solid which
  12. customcrystallised from ether

Sources & evidence

ORD record
ord-3cefd60c7040492d92e8cf0080cba1f7
Source dataset
uspto-grants-2000_08
Patent number
US06100258

Reaction notes

Loading…