Cyclobutanecarboxylic acid → 3,6-Dichloro-4-cyclobutylpyridazine

HRID 1596201Notes

Reaction equation

HRID 1596201 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5]([Cl:8])=[CH:6][CH:7]=1.[CH:9]1(C(O)=O)[CH2:12][CH2:11][CH2:10]1>O.OS(O)(=O)=O>[Cl:1][C:2]1[N:3]=[N:4][C:5]([Cl:8])=[CH:6][C:7]=1[CH:9]1[CH2:12][CH2:11][CH2:10]1

Participants

5

Reactant 2

HCID 19494Cyclobutanecarboxylic acidHCID 673313,6-Dichloropyridazine

Product 1

HCID 219732193,6-Dichloro-4-cyclobutylpyridazineYield 98.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
70 °C

Procedure

3,6-Dichloropyridazine (10 g) was suspended in water (200 ml) and H2SO4 (19.7 g), cyclobutane carboxylic acid (32.7 g) was added and the reaction degassed under N2 at 70° C. Silver nitrate (2.28 g) was added followed by dropwise addition of ammonium persulfate (45.9 g) in water (120 ml). After an additional 1 h heating at 70° C., the reaction was poured onto ice, basified to pH 8-9 with aqueous ammonium hydroxide and extracted into ethyl acetate (3×500 ml), dried (MgSO4) and evaporated to dryness. Purified with hexane-ethyl acetate mixtures to obtain pure product (13.4 g). 1NMR (360 MHz, CDCl3) δ1.57 (2H, m), 1.82 (4H, m), 2.20 (1H, m), 3.30 (1H, m), 7.38 (1H, s); MS (ES+) m/e 217 [MH]+.

Workup

  1. customthe reaction degassed under N2 at 70° C
  2. additionSilver nitrate (2.28 g) was added
  3. additionfollowed by dropwise addition of ammonium persulfate (45.9 g) in water (120 ml)
  4. additionthe reaction was poured onto ice
  5. extractionextracted into ethyl acetate (3×500 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated to dryness
  8. customPurified with hexane-ethyl acetate mixtures

Sources & evidence

ORD record
ord-2ac0d8ad3dd04e358b29d76a43a8a706
Source dataset
uspto-grants-2001_09
Patent number
US06291460B1

Reaction notes

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