Hydrogen Bromide → 6-(4-Bromo-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one

HRID 2199132Notes

Reaction equation

HRID 2199132 reaction equation
N[C:2]1[CH:18]=[C:17]([Cl:19])[C:5]([CH2:6][C:7]2[CH:8]=[C:9]([CH:14]([CH3:16])[CH3:15])[C:10](=[O:13])[NH:11][N:12]=2)=[C:4]([Cl:20])[CH:3]=1.S(=O)(=O)(O)O.N([O-])=O.[Na+].[BrH:30]>C(O)(=O)C.O.[Cu]Br>[Br:30][C:2]1[CH:18]=[C:17]([Cl:19])[C:5]([CH2:6][C:7]2[CH:8]=[C:9]([CH:14]([CH3:16])[CH3:15])[C:10](=[O:13])[NH:11][N:12]=2)=[C:4]([Cl:20])[CH:3]=1

Participants

8

Reactant 4

HCID 260Hydrogen BromideHCID 1118Sulfuric AcidHCID 23668193Sodium NitriteHCID 598344496-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-2H-pyridazin-3-one

Product 1

HCID 598344996-(4-Bromo-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-oneYield 51%

Reagents, catalysts & solvents 3

HCID 24593copper(I) bromideCatalystHCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
60 °C

Procedure

A solution of 6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one (46) (0.9 g, 2.88 mmol) in glacial acetic acid (16 mL) at room temperature was treated with concentrated sulfuric acid (4 mL). A solution of sodium nitrite (480 mg, 6.96 mmol) in water (5 mL) was added below the surface of the reaction slowly over 10 min. The reaction mixture was heated to 60° C. for 1 h. The reaction was cooled to room temperature and a mixture of copper(I) bromide (450 mg, 3.14 mmol) and 48% hydrogen bromide in water (2 mL, 17.68 mmol) was added dropwise. The reaction was heated to 100° C. where vigorous gas evolution occurred. After 1 h, the reaction was cooled to room temperature, poured onto ice water (100 mL) and was extracted with ether (3×75 mL). The ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL). The organic layer was separated, dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting solid was purified by flash chromatography using silica gel eluted with a gradient of 4:1 to 2:1 ethyl acetate:hexanes. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 6-(4-bromo-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one (51) (553 mg, 51%) as an off-white solid; LRMS-ES(+) for C14H13BrCl2N2O (M+H) m/z=375. MW=376.0825, Exact Mass=373.9588

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. additionwas added dropwise
  3. temperatureThe reaction was heated to 100° C. where vigorous gas evolution
  4. temperaturethe reaction was cooled to room temperature
  5. additionpoured onto ice water (100 mL)
  6. extractionwas extracted with ether (3×75 mL)
  7. washThe ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL)
  8. customThe organic layer was separated
  9. dry with materialdried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customThe resulting solid was purified by flash chromatography
  13. washeluted with a gradient of 4:1 to 2:1 ethyl acetate
  14. customThe desired fractions were collected
  15. concentrationconcentrated under vacuum
  16. customto afford a solid which
  17. customwas dried under high vacuum

Sources & evidence

ORD record
ord-cc2362db5dde4d96a360a05d904b6dca
Source dataset
uspto-grants-2016_06
Patent number
USRE046024E1

Reaction notes

Loading…