Acetonitrile → HCID 22291339, compound

HRID 967749Notes

Reaction equation

HRID 967749 reaction equation
Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.C(N(CC)CC)C.[C:14]([C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)#[CH:15].C(#N)C>COCCOC.[Cu]I.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>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:14]#[C:15][C:2]2[S:3][CH:4]=[CH:5][N:6]=2)=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 6342Acetonitrile2×HCID 8471TriethylamineHCID 764302-BromothiazoleHCID 5226271-Ethynyl-4-fluorobenzene

Product 1

HCID 22291339HCID 22291339, compoundYield 3.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

2-Bromo-1,3-thiazole (1.0 g, 6.2 mmol) and CuI (152.4 mg, 0.8 mmol) were combined in DME (17 mL) and argon gas was bubbled through the suspension for several minutes to deoxygenate the mixture. Triethylamine (3 mL, 21 mmol) and PdCl2(PPh3)2 (280 mg, 0.40 mmol) were added and 1-ethynyl-4-fluorobenzene (500 mg, 4.2 mmol) was added dropwise. The reaction was heated under reflux for 4 h at which time GC/MS showed the reaction was complete. The mixture was filtered through Celite™, and the filter pad was washed thoroughly with Ethyl acetate. The combined filtrates were then concentrated in vacuo. The residue was dissolved in ethyl acetate (100 mL), washed with water (100 mL), brine (100 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with hexane then 98:2 hexane:ethyl acetate to 2-[(4-fluorophenyl)ethynyl]-1,3-thiazole as a white solid which was impure by 1H NMR analysis. The compound (280 mg) was dissolved in DMSO and purified by preparative HPLC with a 30 min gradient from 60:40 water:acetonitrile to 100% acetonitrile to afford 2-[(4-fluorophenyl)ethynyl]-1,3-thiazole (33 mg, 3% yield) as a white solid. M.p. 78–79° C. 1H NMR (CDCl3, 300 MHz) δ 7.83 (d, J=3.0 Hz, 1H), 7.60–7.55(m, 2H), 7.39 (d, J=3.0 Hz, 1H), 7.14–7.00 (m, 2H). MS (ESI) 204 (M++H).

Workup

  1. customargon gas was bubbled through the suspension for several minutes
  2. customto deoxygenate the mixture
  3. temperatureThe reaction was heated
  4. temperatureunder reflux for 4 h at which time GC/MS
  5. filtrationThe mixture was filtered through Celite™
  6. washthe filter pad was washed thoroughly with Ethyl acetate
  7. concentrationThe combined filtrates were then concentrated in vacuo
  8. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  9. washwashed with water (100 mL), brine (100 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by column chromatography
  14. washeluting with hexane
  15. dissolutionThe compound (280 mg) was dissolved in DMSO
  16. custompurified by preparative HPLC with a 30 min gradient from 60:40 water

Sources & evidence

ORD record
ord-34bcb57e5d2d484c9a1fef5c2c08259c
Source dataset
uspto-grants-2005_10
Patent number
US06956049B1

Reaction notes

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