3-Bromo-6-propylpyridazine → HCID 178444404, compound

HRID 1982117Notes

Reaction equation

HRID 1982117 reaction equation
Br[C:2]1[N:3]=[N:4][C:5]([CH2:8][CH2:9][CH3:10])=[CH:6][CH:7]=1.[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:15][CH2:14]1)#[CH:12]>C(N(CC)CC)C.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.[Cu]I>[CH2:19]([C@H:16]1[CH2:15][CH2:14][C@H:13]([C:11]#[C:12][C:2]2[N:3]=[N:4][C:5]([CH2:8][CH2:9][CH3:10])=[CH:6][CH:7]=2)[CH2:18][CH2:17]1)[CH2:20][CH2:21][CH2:22][CH3:23]

Participants

6

Reactant 2

HCID 233171853-Bromo-6-propylpyridazineHCID 178455744HCID 178455744, compound

Product 1

HCID 178444404HCID 178444404, compoundYield 43.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

8.0 g of 3-bromo-6-propylpyridazine were dissolved in 50 ml of triethylamine in a sulphonation flask under nitrogen. The solution was cooled to 0° C., treated with 562 mg of bis-(triphenylphosphine)-palladium (II) dichloride and 76 mg of copper (I) iodide and then treated dropwise within 20 minutes with 7.5 g of trans-1-ethynyl-4-pentylcyclohexane (prepared according to Example 2). The mixture was subsequently stirred overnight while cooling with an ice-bath and then heated to 50° C. for a further 3 hours. The mixture was concentrated on a rotary evaporator. The residue was taken up in 100 ml of hexane and washed with 100 ml of water, whereby the pH value of the aqueous phase was made neutral with ammonium chloride. The aqueous phase was back-extracted twice with 50 ml of hexane each time. The combined organic phases were washed with 100 ml of water and the aqueous phase was back-extracted with 50 ml of hexane. The organic phases were dried over sodium sulphate and freed from solvent on a rotary evaporator. Chromatography of the resulting brown crystallizing oil on silica gel with hexane/ethyl acetate (vol. 2:1) gave a fraction of the desired product 3-[2-(trans-4-pentylcyclohexyl)ethynyl]-6-propylpyridazine (5.2 g) as well as a mixed fraction (4.8 g) consisting of 3-bromo-6-propylpyridazine and product. The pure fraction was recrystallized from 15 ml of ethanol at -20° C. There were thus obtained 4.0 g of white crystals which were recrystallized from 25 ml of pentane at -20° C. The crystals were subsequently dried for 2 hours in a vacuum drying oven at 40° C. and then overnight at room temperature with a slight stream of nitrogen in a high vacuum, there being obtained 3.4 g of 3-[2-(trans-4-pentylcyclohexyl)ethynyl]-6-propylpyridazine as white crystals of melting point (C-I) 118°-118.5° C.

Workup

  1. temperaturewhile cooling with an ice-bath
  2. temperatureheated to 50° C. for a further 3 hours
  3. concentrationThe mixture was concentrated on a rotary evaporator
  4. washwashed with 100 ml of water, whereby the pH value of the aqueous phase
  5. extractionThe aqueous phase was back-extracted twice with 50 ml of hexane each time
  6. washThe combined organic phases were washed with 100 ml of water
  7. extractionthe aqueous phase was back-extracted with 50 ml of hexane
  8. dry with materialThe organic phases were dried over sodium sulphate
  9. customfreed from solvent on a rotary evaporator
  10. customChromatography of the resulting brown crystallizing oil on silica gel with hexane/ethyl acetate (vol. 2:1)

Sources & evidence

ORD record
ord-c8f01e2a84534dd88f428aa728e9fb23
Source dataset
uspto-grants-1986_06
Patent number
US04595521

Reaction notes

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