Propargyl alcohol → 3-Quinolin-3-ylprop-2-yn-1-ol

HRID 2304766Notes

Reaction equation

HRID 2304766 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[CH2:12]([OH:15])[C:13]#[CH:14].C(N(CC)CC)C>C([O-])(O)=O.[Na+].[Cu]I>[N:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH:11]=[C:2]([C:14]#[C:13][CH2:12][OH:15])[CH:3]=1

Participants

6

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 214133-Bromoquinoline

Product 1

HCID 6501423-Quinolin-3-ylprop-2-yn-1-olYield 88.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 516892Sodium BicarbonateSolvent

Procedure

To a dry 2-L three-necked flask previously purged with nitrogen, was charged 3-bromoquinoline (118.77 g, 570 mmol), propargyl alcohol (71.9 g, 1.28 mol, 2.25 equiv), triethylamine (1500 mL), copper(I) iodide (3.62 g, 19 mmol, 0.033 equiv) and dichlorobis(triphenylphosphine) palladium(II) (6.67 g, 9.5 mmol). The resulting mixture was mechanically stirred and heated to reflux for 3 hours. Upon cooling, the triethylamine solution was filtered and washed with triethylamine (300 mL). The filtrate was then concentrated under reduced pressure to provide solids which were suspended in 5% aq. NaHCO3 (600 mL) and extracted with ethyl acetate (1×600 mL). The solids which were left after filtration were treated in the same manner (i.e., suspend in aq. 5% NaHCO3 and extracted with ethyl acetate). The combined ethyl acetate extracts were stirred with silica gel (15 g) and decolorizing carbon (3 g) before being filtered through a bed of diatomaceous earth. The filtrate was concentrated under reduced pressure to provide a tan colored solid which was dried in the vacuum oven at 45° C. overnight. The 3-(3-quinolyl)-2-propyn-1-ol was thus isolated. 92.14 g, 88.3% yield. MS(Cl): (M+H)+ at 184; NMR (300 MHz CDCl3) δ: 4.58 (s, 2H), 4.70 (s, broad, 1H), 7.57 (m,1H), 7.70 (m, 1H), 7.77 (d, 1H), 8.10 (d, 1H), 8.10 (s, H), 9.05 (s, 1H).

Workup

  1. customTo a dry 2-L three-necked flask previously purged with nitrogen
  2. temperatureheated
  3. temperatureto reflux for 3 hours
  4. temperatureUpon cooling
  5. filtrationthe triethylamine solution was filtered
  6. washwashed with triethylamine (300 mL)
  7. concentrationThe filtrate was then concentrated under reduced pressure
  8. customto provide solids which
  9. extractionextracted with ethyl acetate (1×600 mL)
  10. waitThe solids which were left
  11. filtrationafter filtration
  12. additionwere treated in the same manner (i.e., suspend in aq. 5% NaHCO3 and extracted with ethyl acetate)
  13. stirringThe combined ethyl acetate extracts were stirred with silica gel (15 g)
  14. filtrationbefore being filtered through a bed of diatomaceous earth
  15. concentrationThe filtrate was concentrated under reduced pressure
  16. customto provide a tan colored solid which
  17. customwas dried in the vacuum oven at 45° C. overnight

Sources & evidence

ORD record
ord-5e7740789ae84dc6b5f6e8de79c147a0
Source dataset
uspto-grants-2002_08
Patent number
US06437106B1

Reaction notes

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