N-methyl-2-pyrrolidone → 4-Chloro-1-(4-methylbenzene-1-sulfonyl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine

HRID 490275Notes

Reaction equation

HRID 490275 reaction equation
[F-].[K+].CN1C(=O)CCC1.[Cl:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]2[N:17]([S:21]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:18]=[C:19](I)[C:12]=12.C[Si](C)(C)[C:33]([F:36])([F:35])[F:34]>[Cu]I.C(OC)(C)(C)C.CN(C=O)C>[Cl:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]2[N:17]([S:21]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)(=[O:23])=[O:22])[CH:18]=[C:19]([C:33]([F:36])([F:35])[F:34])[C:12]=12

Participants

8

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 522689Potassium Fluoride2×HCID 552549(Trifluoromethyl)trimethylsilaneHCID 534382524-Chloro-3-iodo-1-(4-methylbenzene-1-sulfonyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 116893174-Chloro-1-(4-methylbenzene-1-sulfonyl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridineYield 67.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
220 °C

Procedure

Under protective gas atmosphere (argon), 23.1 g (0.398 mol) of dry potassium fluoride and 75.7 g (0.398 mol) of copper(I) iodide were titrated together and heated to 220° C. under high vacuum with agitation for 10 minutes until a slightly greenish colouration appeared. A reaction flask was initially charged under protective gas atmosphere (argon) with the calcined mixture of potassium fluoride and copper(I) iodide together with 170 ml of absolute NMP and 170 ml of absolute DMF, and 86 g (0.199 mol) of 4-chloro-1-(toluene-4-sulphonyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine were subsequently introduced in portions at 20° C. with stirring to form a light grey suspension. 62.1 g (0.437 mol) of trimethyltrifluoromethylsilane were added dropwise to the reaction mixture within 20 minutes and the mixture was left to stir at 20° C. for 18 h. On completion of conversion (GC monitoring of conversion), the reaction mixture was added to 2000 ml of methyl tert-butyl ether, the organic phase was decanted and the residue was dispersed once more with 1000 ml of methyl tert-butyl ether. The combined organic phases were washed three times with 2000 ml each time of water and subsequently dried over MgSO4. Filtration and removal of the volatile constituents in a water-jet vacuum resulted in 50.1 g (0.134 mol; 67%) of 4-chloro-1-(toluene-4-sulphonyl)-3-trifluoromethyl-1H-pyrrolo[2,3-b]pyridine as a beige solid.

Workup

  1. additionwere subsequently introduced in portions at 20° C.
  2. customto form a light grey suspension
  3. waitthe mixture was left
  4. stirringto stir at 20° C. for 18 h
  5. customthe organic phase was decanted
  6. additionthe residue was dispersed once more with 1000 ml of methyl tert-butyl ether
  7. washThe combined organic phases were washed three times with 2000 ml each time of water
  8. dry with materialsubsequently dried over MgSO4
  9. filtrationFiltration and removal of the volatile constituents in a water-jet vacuum

Sources & evidence

ORD record
ord-e97a8221d2e0457ba5ca59da07b5acf2
Source dataset
uspto-grants-2009_05
Patent number
US07528146B2

Reaction notes

Loading…