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

HRID 1370010

Reaction equation

HRID 1370010 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 8471Triethylamine2×HCID 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, 19 mmol, 0.033 equiv) and dichlorobis(triphenyl-phosphine) palladium(II) (6.67 g, 9.5 mmol). The mixture which resulted was mechanically stirred and heated to reflux for 3 hours. Upon cooling the triethylamine solution 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. The combined ethyl acetate extracts were stirred with silica gel (15 g) and decolorizing carbon (3 g) before being filtered through a bed of celite. The filtrate was concentrated under reduced pressure to provide a tan colored solid which was vacuum oven dried at 45° C. overnight. The 3-(3-quinolyl)-2-propyn-1-ol was isolated in 92.14 g (88.3% yield). MS(CI): (M+H)+ at 184; 1H NMR (300 MHz CDCl3) δ4.56 (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, 1H), 9.05 (s, 1H).

Workup

  1. customTo a dry 2-L three-necked flask previously purged with nitrogen
  2. customThe mixture which resulted
  3. temperatureheated
  4. temperatureto reflux for 3 hours
  5. stirringwas mechanically stirred
  6. temperatureheated
  7. temperatureto reflux for 3 hours
  8. temperatureUpon cooling
  9. filtrationthe triethylamine solution was filtered
  10. washwashed with triethylamine (300 mL)
  11. concentrationThe filtrate was then concentrated under reduced pressure
  12. customto provide solids which
  13. extractionextracted with ethyl acetate (1×600 mL)
  14. waitThe solids which were left
  15. filtrationafter filtration
  16. additionwere treated in the same manner
  17. stirringThe combined ethyl acetate extracts were stirred with silica gel (15 g)
  18. filtrationbefore being filtered through a bed of celite
  19. concentrationThe filtrate was concentrated under reduced pressure
  20. customto provide a tan colored solid which
  21. customdried at 45° C. overnight

Sources & evidence

ORD record
ord-a463d10a1a0543899f2879ce00cf2124
Source dataset
uspto-grants-2003_06
Patent number
US06579986B2

Linked notes

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