1-Chloro-3-iodobenzene → 3,4-Bis(benzyloxy)-6-((3-chlorophenyl)ethynyl)pyridazine

HRID 927077Notes

Reaction equation

HRID 927077 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](I)[CH:3]=1.N1(C2CCCCCCCCCC2)CCCN=CCCCCC1.C1CCN2C(=NCCC2)CC1.[CH2:42]([O:49][C:50]1[N:51]=[N:52][C:53]([C:64]#[CH:65])=[CH:54][C:55]=1[O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>O1CCCC1.[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>[CH2:42]([O:49][C:50]1[N:51]=[N:52][C:53]([C:64]#[C:65][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)=[CH:54][C:55]=1[O:56][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1

Participants

8

Reactant 4

HCID 122691-Chloro-3-iodobenzeneHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 866770253,4-Bis(benzyloxy)-6-ethynylpyridazine2×HCID 1296629601,8-Diazabicycloundec-7ene

Product 1

HCID 712699503,4-Bis(benzyloxy)-6-((3-chlorophenyl)ethynyl)pyridazineYield 30%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

To a solution of 1-chloro-3-iodobenzene (0.862 g, 3.62 mmol) in dry tetrahydrofuran (11 ml) was added copper(I) iodide (0.063 g, 0.33 mmol), bis(triphenylphosphine)-palladium(II) chloride (0.115 g, 0.16 mmol) and 1,8-diazabicycloundec-7-ene and (DBU; 2.97 ml, 19.72 mmol). The reaction was then purged and evacuated with nitrogen several times before 3,4-bis(benzyloxy)-6-ethynylpyridazine (Intermediate 5; 1.04 g, 3.29 mmol) was added. The reaction vessel was sealed and heated to 80° C. for 1 hour. Upon cooling, the resultant mixture was partitioned between ethyl acetate and water. The combined organic portions were washed with water (×2) and brine, dried (MgSO4), filtered and concentrated to give a brown oil. The crude oil was purified by silica chromatography (eluting with 0-20% ethyl acetate in petrol) to yield 3,4-bis(benzyloxy)-6-((3-chlorophenyl)ethynyl)pyridazine as a yellow solid (yield=30%).

Workup

  1. customThe reaction was then purged
  2. additionwas added
  3. customThe reaction vessel was sealed
  4. temperatureUpon cooling
  5. customthe resultant mixture was partitioned between ethyl acetate and water
  6. washThe combined organic portions were washed with water (×2) and brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a brown oil
  11. customThe crude oil was purified by silica chromatography (eluting with 0-20% ethyl acetate in petrol)

Sources & evidence

ORD record
ord-38160e5aef3340c1881c66303169bfe1
Source dataset
uspto-grants-2016_03
Patent number
US09290456B2

Reaction notes

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