Dichloromethane → 8-(3-Pyridinyl)-7-octyn-1-ol

HRID 1249580Notes

Reaction equation

HRID 1249580 reaction equation
C(Cl)Cl.[CH2:4]([OH:12])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]#[CH:11].Br[C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1>C(N(CC)CC)C>[N:16]1[CH:17]=[CH:18][CH:19]=[C:14]([C:11]#[C:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][OH:12])[CH:15]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 122863-Bromopyridine2×HCID 701007-Octyn-1-ol

Product 1

HCID 137545048-(3-Pyridinyl)-7-octyn-1-olYield 91.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

A flame-dried, 22-L flask equipped with a mechanical stirrer, condenser, and a gas inlet tube dipping below the surface of the solvent was charged with 4.0 L of methylene chloride, 1.25 L of triethylamine, 385 g of 7-octyn-1-ol, and 285 mL (456 g) of 3-bromopyridine. The reagents were rinsed into the flask with an additional 100 mL of methylene chloride. Argon was bubbled through the reaction mixture for 30 minutes. The flask was evacuated for 3 minutes at 70 mm. The vacuum was released by bubbling in argon. This process was repeated six times and then 42 g of dichlorobis(triphenyl phosphine)palladium (II) and 4 g of cuprous iodide were added. The mixture was heated at a gentle reflux for 18 hours and cooled to 20°. To the mixture was added, with vigorous stirring, 8.0 L of ether. A small amount of yellowish-white solid was removed by filtration and washed with 2×1.5 L=3.0 L of ether. The combined filtrate was washed with 3.0 L of deionized water and 2×3.0 L=6.0 L of 1N hydrochloric acid. The combined aqueous solutions were washed with 2×2.5 L=5.0 L of ether. The organic solutions were discarded and the aqueous solution was made strongly basic by the addition of 2.50 L of 20% sodium hydroxide solution. The resulting mixture was extracted with 3×4.0 L=12.0 L of methylene chloride. The extracts were dried over sodium sulfate and filtered through Celite. Solvent removal on a rotary evaporator at 45° gave 534.2 g (91% yield) of a pale brown 8-(3-pyridinyl)-7-octyn-1-ol having a strong odor of 3-bromopyridine. No further purification of this material was undertaken.

Workup

  1. washThe reagents were rinsed into the flask with an additional 100 mL of methylene chloride
  2. customArgon was bubbled through the reaction mixture for 30 minutes
  3. customThe flask was evacuated for 3 minutes at 70 mm
  4. customby bubbling in argon
  5. addition42 g of dichlorobis(triphenyl phosphine)palladium (II) and 4 g of cuprous iodide were added
  6. temperatureThe mixture was heated at
  7. temperaturea gentle reflux for 18 hours
  8. temperaturecooled to 20°
  9. additionTo the mixture was added, with vigorous stirring, 8.0 L of ether
  10. customA small amount of yellowish-white solid was removed by filtration
  11. washwashed with 2×1.5 L=3.0 L of ether
  12. washThe combined filtrate was washed with 3.0 L of deionized water and 2×3.0 L=6.0 L of 1N hydrochloric acid
  13. washThe combined aqueous solutions were washed with 2×2.5 L=5.0 L of ether
  14. additionthe aqueous solution was made strongly basic by the addition of 2.50 L of 20% sodium hydroxide solution
  15. extractionThe resulting mixture was extracted with 3×4.0 L=12.0 L of methylene chloride
  16. dry with materialThe extracts were dried over sodium sulfate
  17. filtrationfiltered through Celite
  18. customSolvent removal
  19. customon a rotary evaporator at 45°

Sources & evidence

ORD record
ord-90f8a98ca6a94414b1d6fffcb8ef996c
Source dataset
uspto-grants-1986_12
Patent number
US04632925

Reaction notes

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