1,2-Dibromoethane → 3-cyclobutyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

HRID 2196697Notes

Reaction equation

HRID 2196697 reaction equation
[Mg].Br[CH:3]1[CH2:6][CH2:5][CH2:4]1.BrCCBr.Br[C:12]1[C:20]2[C:15](=[N:16][CH:17]=[CH:18][CH:19]=2)[N:14]([S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH:13]=1>C1COCC1.CCOCC>[CH:3]1([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[CH:18][CH:19]=3)[N:14]([S:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)(=[O:23])=[O:22])[CH:13]=2)[CH2:6][CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 78391,2-DibromoethaneHCID 78110BromocyclobutaneHCID 5462224MagnesiumHCID 455881343-Bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 671563403-cyclobutyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridineYield 19.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A round bottom flask under a nitrogen atmosphere was charged with magnesium turnings (155 mg, 6.38 mmol) and dry ether (5 mL). Bromocyclobutane (340 mg, 2.52 mmol) was added, followed by 1,2-dibromoethane (50 μL) and refluxing was observed after a few minutes of stirring. This mixture was then warmed back to reflux for 5 hours and then allowed to cool to room temperature. The Grignard reagent was then added to a THF solution (5 mL) of 3-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (250 mg, 0.74 mmol) and NiCl2(dppf) (10 mg, 0.015 mmol). The mixture was heated at reflux for 16 hours and then allowed to cool to room temperature. The reaction mixture was quenched with saturated ammonium chloride solution and extracted with EtOAc (2×). The extracts were dried over sodium sulfate and concentrated. Flash 40 Biotage (40M cartridge, 3:1 hexane:EtOAc) afforded 3-cyclobutyl-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (45 mg, 19%). m/z (APCI-pos) M+1=313.1.

Workup

  1. temperaturerefluxing
  2. waitwas observed after a few minutes
  3. temperatureThis mixture was then warmed back
  4. temperatureto reflux for 5 hours
  5. temperatureThe mixture was heated
  6. temperatureat reflux for 16 hours
  7. temperatureto cool to room temperature
  8. customThe reaction mixture was quenched with saturated ammonium chloride solution
  9. extractionextracted with EtOAc (2×)
  10. dry with materialThe extracts were dried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-fcec88003461448cbe8a90ed993e3379
Source dataset
uspto-grants-2012_12
Patent number
US08338452B2

Reaction notes

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