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

HRID 2240256Notes

Reaction equation

HRID 2240256 reaction equation
[F-].[K+].CN1CCCC1.[Cl:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[N:16]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH:17]=[C:18](I)[C:11]=12.C[Si](C)(C)[C:32]([F:35])([F:34])[F:33]>[Cu]I.C(OC)(C)(C)C.CN(C=O)C>[Cl:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]2[N:16]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH:17]=[C:18]([C:32]([F:35])([F:34])[F:33])[C:11]=12

Participants

8

Reactant 4

HCID 84541-MethylpyrrolidineHCID 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]pyridine

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 an atmosphere of protective gas (argon), 23.1 g (0.398 mol) of dry potassium fluoride and 75.7 g (0.398 mol) of copper(I) iodide are ground with one another and, under high vacuum and with shaking, heated at 220° C. for 10 minutes, until there is a slight greenish discoloration. The sintered mixture of potassium fluoride and copper(1) iodide together with 170 ml of absolute N-methylpyrrolidine and 170 ml of absolute DMF is initially charged in a reaction flask under an atmosphere of protective gas (argon), and 86 g (0.199 mol) of 4-chloro-1-(toluene-4-sulfonyl)-3-iodo-1H-pyrrolo[2,3-b]pyridine are then added a little at a time and with stirring at 20° C., whereupon a light-gray suspension is formed. Over a period of 20 minutes, 62.1 g (0.437 mol) of trimethyltrifluoromethylsilane are added dropwise to the reaction mixture, and the mixture is stirred at 20° C. for 18 h. After complete conversion (conversion monitored by GC), the reaction mixture is poured into 2000 ml of methyl tert-butyl ether, the organic phase is decanted and the residue is once more dispersed in 1000 ml of methyl tert-butyl ether. The combined organic phases are washed three times with in each case 2000 ml of water and then dried over magnesium sulfate. Filtration and removal of the volatile components under water pump vacuum gives 50.1 g (67% of theory) of the target compound as a solid.

Workup

  1. additionare then added a little at a time
  2. stirringwith stirring at 20° C., whereupon a light-gray suspension
  3. customis formed
  4. stirringthe mixture is stirred at 20° C. for 18 h
  5. customthe organic phase is decanted
  6. additionthe residue is once more dispersed in 1000 ml of methyl tert-butyl ether
  7. washThe combined organic phases are washed three times with in each case 2000 ml of water
  8. dry with materialdried over magnesium sulfate
  9. filtrationFiltration and removal of the volatile components under water pump vacuum

Sources & evidence

ORD record
ord-375c887bfd35490c8b7a3a5e342920dd
Source dataset
uspto-grants-2010_05
Patent number
US07723347B2

Reaction notes

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