4-Bromo-2-methyl-1-(trifluoromethyl)benzene → 3,4-Bis(benzyloxy)-6-((3-methyl-4-(trifluoromethyl)phenyl)-ethynyl)pyridazine

HRID 927122

Reaction equation

HRID 927122 reaction equation
[CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12]([C:23]#[CH:24])=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[C:28]([CH3:36])[CH:27]=1.N1(C2CCCCCCCCCC2)CCCN=CCCCCC1>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH2:1]([O:8][C:9]1[N:10]=[N:11][C:12]([C:23]#[C:24][C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:33])([F:35])[F:34])=[C:28]([CH3:36])[CH:27]=2)=[CH:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 457904784-Bromo-2-methyl-1-(trifluoromethyl)benzeneHCID 866770253,4-Bis(benzyloxy)-6-ethynylpyridazine2×HCID 1296629601,8-Diazabicycloundec-7ene

Product 1

HCID 712698973,4-Bis(benzyloxy)-6-((3-methyl-4-(trifluoromethyl)phenyl)-ethynyl)pyridazineYield 27.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

3,4-bis(Benzyloxy)-6-ethynylpyridazine (Intermediate 5; 3.0 g, 9.48 mmol), copper(I) iodide (0.181 g, 0.948 mmol) and bis(triphenylphosphine)-palladium(II) dichloride (0.333 g, 0.474 mmol) were combined. The reaction vessel was purged with nitrogen, followed by the addition of 4-bromo-2-methyl-1-(trifluoromethyl)benzene (2.493 g, 10.43 mmol), 1,8-diazabicycloundec-7-ene (8.66 g, 56.9 mmol) and tetrahydrofuran (32 ml) before the resulting mixture was allowed to stir at room temperature overnight. The reaction was quenched with brine and extracted into ethyl acetate (×2) and the combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo to afford a dark brown gum. The gum was purified by column chromatography (silica, 0-50% ethyl acetate in petrol) to afford 3,4-bis(benzyloxy)-6-((3-methyl-4-(trifluoromethyl)phenyl)-ethynyl)pyridazine as a dark brown oil (1.22 g, 27%).

Workup

  1. customThe reaction vessel was purged with nitrogen
  2. customThe reaction was quenched with brine
  3. extractionextracted into ethyl acetate (×2)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customto afford a dark brown gum
  8. customThe gum was purified by column chromatography (silica, 0-50% ethyl acetate in petrol)

Sources & evidence

ORD record
ord-594ce1e37bab4f0a90d50822147e048c
Source dataset
uspto-grants-2016_03
Patent number
US09290456B2

Linked notes

Loading…