Triphenylphosphine → 2-(4'-Fluorophenyl)-4-[4'-(3-dimethylamino-2-propyn-1-yl)phenyl]thiazole

HRID 650996Notes

Reaction equation

HRID 650996 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[S:28][CH:29]=[C:30]([C:32]3[CH:37]=[CH:36][C:35](Br)=[CH:34][CH:33]=3)[N:31]=2)=[CH:23][CH:22]=1.[CH3:39][N:40]([CH3:44])[CH2:41][C:42]#[CH:43]>C(NCC)C.C(#N)C.Cl[Pd]Cl.[Cu]I>[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[S:28][CH:29]=[C:30]([C:32]3[CH:37]=[CH:36][C:35]([CH2:43][C:42]#[C:41][N:40]([CH3:44])[CH3:39])=[CH:34][CH:33]=3)[N:31]=2)=[CH:23][CH:22]=1

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 81643N,N-DimethylpropargylamineHCID 111749984-(4-Bromo-phenyl)-2-(4-fluoro-phenyl)-thiazole

Product 1

HCID 226110582-(4'-Fluorophenyl)-4-[4'-(3-dimethylamino-2-propyn-1-yl)phenyl]thiazole

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolventHCID 8021DiethylamineSolvent

Procedure

In a 100 ml flask is placed triphenylphosphine (80 mg, 10%), PdCl2 (40 mg, 5%) and 2-(4′-fluorophenyl)-4-(4′-bromophenyl)thiazole (0.98 g, 2.9 mmol) in 20 mL of diethylamine. After stirring for 15 min under N2 atmosphere, CuI (30 mg, 5%) and 1-dimethylamino-2-propyne (0.27 g, 3.18 mmol) in 20 ml of acetonitrile are added to the mixture. After 18 h of heating, the solvent is evaporated under reduced pressure and the residue is filtered through silica gel pad (50 g) using CHCl3 (400 mL) and 2% MeOH in CHCl3(400 mL). A large portion of unreacted 2-(4′-fluorophenyl)-4-(4′-bromophenyl)thiazole is recovered after removal of chloroform filtrate (0.55 g, 56%). The second part of the filtrate (2% MeOH in CHCl3) is concentrated and the residual solid is then purified over silica gel column eluting with 2% MeOH in CHCl3. 2-(4′-fluorophenyl)-4-[4′-(3-dimethylamino-2-propyn-1-yl)phenyl]thiazole is obtained after concentration and trituration with hexane (0.25 g, 27% yield), mp. 98-9° C.

Workup

  1. customIn a 100 ml flask is placed
  2. temperatureAfter 18 h of heating
  3. customthe solvent is evaporated under reduced pressure
  4. filtrationthe residue is filtered through silica gel pad (50 g)
  5. customA large portion of unreacted 2-(4′-fluorophenyl)-4-(4′-bromophenyl)thiazole is recovered
  6. customafter removal of chloroform filtrate (0.55 g, 56%)
  7. concentrationThe second part of the filtrate (2% MeOH in CHCl3) is concentrated
  8. customthe residual solid is then purified over silica gel column
  9. washeluting with 2% MeOH in CHCl3

Sources & evidence

ORD record
ord-0b6c614c60de42b8b3beef40aff981ea
Source dataset
uspto-grants-2001_08
Patent number
US06277873B1

Reaction notes

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