4-Methylmorpholine → Ethyl 6-(hydroxymethyl)-3-pyridazinecarboxylate

HRID 1879409Notes

Reaction equation

HRID 1879409 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:11]=[N:10][C:9]([C:12](O)=[O:13])=[CH:8][CH:7]=1)=[O:5])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>C(COC)OC.O>[OH:13][CH2:12][C:9]1[N:10]=[N:11][C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 18441970HCID 18441970, compound

Product 1

HCID 18442007Ethyl 6-(hydroxymethyl)-3-pyridazinecarboxylateYield 45.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
0 °C

Procedure

435 mg of 6-(ethoxycarbonyl)pyridazine-3-carboxylic acid was dissolved in 11.0 mL of dimethoxyethane, and 0.424 mL of 4-methylmorpholine and 0.531 ml, of isobutyl chloroformate were added thereto at 0° C. After stirring at 0° C. for 2 hours, a suspension of 294 mg of sodium borohydride in water (2.50 mL) was added to the reaction liquid, followed by further stiffing at 0° C. for 20 minutes. To the reaction liquid was added water, followed by extraction with ethyl acetate, and the organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (chloroform:methanol=97:3 to 90:10) to obtain 184 mg of ethyl 6-(hydroxymethyl)pyridazine-3-carboxylate.

Workup

  1. customat 0° C
  2. additionwas added to the reaction liquid
  3. waitfollowed by further stiffing at 0° C. for 20 minutes
  4. customTo the reaction liquid
  5. extractionfollowed by extraction with ethyl acetate
  6. washthe organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customThe solvent was evaporated
  9. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol=97:3 to 90:10)

Sources & evidence

ORD record
ord-5de5672e91094243b0c4de5e9a930b47
Source dataset
uspto-grants-2012_11
Patent number
US08314240B2

Reaction notes

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