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

HRID 1982121Notes

Reaction equation

HRID 1982121 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.COC(C)(C)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

7

Reactant 2

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

Product 1

HCID 178444404HCID 178444404, compoundYield 43.8%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
0 °C

Procedure

8.0 g of 3-bromo-6-propylpyridazine (prepared according to Example 3) 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. The mixture was subsequently stirred at 0° C. for several hours, then at room temperature overnight and finally at 50° C. for a further 3 hours. For the working-up, the dark coloured mixture was diluted with 100 ml of tert.butyl methyl ether and suction filtered through a paper filter (rinsing with tert.butyl methyl ether). The filtrate was concentrated on a rotary evaporator. The dark coloured crystalline residue was taken up in 150 ml of tert.butyl methyl ether and washed successively with 100 ml of 2% (wt./vol.) ammonium chloride solution and with 100 ml of water. Each of the aqueous phases were back-extracted with a small amount of tert.butyl methyl ether. The combined organic phases were dried over sodium sulphate and concentrated on a rotary evaporator. For the purification, the brown coloured crystals obtained were chromatographed on silica gel with hexane/ethyl acetate (vol. 2:1), there being obtained a fraction of the desired product 3-[2-(trans-4-pentylcyclohexyl)ethynyl]-6-propylpyridazine (5.2 g) and a mixed fraction consisting of 3-bromo-6-propylpyridazine and product (4.8 g). The pure fraction was recrystallized once from ethanol at -20° C. and once from hexane at -20° C. and finally dried well in a vacuum drying oven at 40° C. There were thus obtained 3.4 g (28.5%) of 3-[2-(trans-4-pentylcyclohexyl)ethynyl]-6-propylpyridazine in the form of white crystals of melting point (C-I) 118.5° C., boiling point 210°-220° C./0.08 Torr.

Workup

  1. filtrationfiltered through a paper
  2. filtrationfilter
  3. wash(rinsing with tert.butyl methyl ether)
  4. concentrationThe filtrate was concentrated on a rotary evaporator
  5. washwashed successively with 100 ml of 2% (wt./vol.) ammonium chloride solution and with 100 ml of water
  6. extractionEach of the aqueous phases were back-extracted with a small amount of tert.butyl methyl ether
  7. dry with materialThe combined organic phases were dried over sodium sulphate
  8. concentrationconcentrated on a rotary evaporator
  9. customFor the purification
  10. customthe brown coloured crystals obtained
  11. customwere chromatographed on silica gel with hexane/ethyl acetate (vol. 2:1), there

Sources & evidence

ORD record
ord-d61fcb66abf2460d81cb6895305a4d5c
Source dataset
uspto-grants-1986_06
Patent number
US04595521

Reaction notes

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