Propyne → HCID 20616790, compound

HRID 2404372Notes

Reaction equation

HRID 2404372 reaction equation
CC[N:3]([CH2:6][CH3:7])[CH2:4][CH3:5].Br[C:9]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:10]=1C=O.C#CC.N.CO.C1C2C(=CC=CC=2)C=CN=1>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.CN(C=O)C>[F:17][C:15]1[CH:14]=[C:13]2[C:5](=[CH:9][CH:16]=1)[CH:4]=[N:3][C:6]([CH3:7])=[CH:10]2

Participants

9

Reactant 5

HCID 6335PropyneHCID 8405IsoquinolineHCID 8471TriethylamineHCID 27733192-Bromo-4-fluorobenzaldehydeHCID 21705897Ammonia methanol

Product 1

HCID 20616790HCID 20616790, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

DMF (50 mL) and NEt3 (10.30 mL, 73.9 mmol) were added to 2-bromo-4-fluorobenzaldehyde (10 g, 49.3 mmol) under argon in a 300 mL stainless steel reactor. The vessel was sparged with propyne and chilled in dry ice, then propyne (18.22 mL, 296 mmol) was distilled in. Bis(triphenylphosphine)palladium(II) chloride (0.173 g, 0.246 mmol) and copper(I) iodide (0.047 g, 0.246 mmol) were added, and the reactor was sealed and stirred for 4 hours at room temperature. The mixture was chilled and sampled. HPLC analysis indicated 90% conversion. 2 M NH3/MeOH (150 mL) was added to the chilled (and solidified) mixture, and the resulting solution was stirred 1.5 hours at 85° C. HPLC indicated complete conversion of alkyne to isoquinoline. The mixture was cooled and concentrated. Water (200 mL) and EtOAc (200 mL) were added, the layers were separated, and the organic layer was washed with brine (2×50 mL). The organic portion was extracted with 2N HCl (100 mL) and water (100 mL), then the aqueous layer was basified with 2N NaOH (120 mL). The mixture was extracted with EtOAc (2×100 mL) and the organic layer was washed with brine (50 mL), dried (Na2SO4), and concentrated, giving the title compound (6.87 g, 42.6 mmol, 87% yield). MS (DCI/NH3) m/z 162 (M+H)+.

Workup

  1. customThe vessel was sparged with propyne
  2. temperaturechilled in dry ice
  3. customthe reactor was sealed
  4. temperatureThe mixture was chilled
  5. aliquotsampled
  6. temperaturechilled (and solidified) mixture
  7. stirringthe resulting solution was stirred 1.5 hours at 85° C
  8. temperatureThe mixture was cooled
  9. concentrationconcentrated
  10. additionWater (200 mL) and EtOAc (200 mL) were added
  11. customthe layers were separated
  12. washthe organic layer was washed with brine (2×50 mL)
  13. extractionThe organic portion was extracted with 2N HCl (100 mL) and water (100 mL)
  14. extractionThe mixture was extracted with EtOAc (2×100 mL)
  15. washthe organic layer was washed with brine (50 mL)
  16. dry with materialdried (Na2SO4)
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-020ac41d7a724a9c8d9e3ba33cc8b33b
Source dataset
uspto-grants-2014_08
Patent number
US08802711B2

Reaction notes

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