Sodium Carbonate → 5-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one

HRID 493146Notes

Reaction equation

HRID 493146 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH2:10][C:9](=[O:11])[NH:8][C:5]2=[N:6][CH:7]=1.[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1.[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>CCO.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.C1(C)C=CC=CC=1>[F:12][C:13]1[CH:18]=[C:17]([C:2]2[CH:3]=[C:4]3[CH2:10][C:9](=[O:11])[NH:8][C:5]3=[N:6][CH:7]=2)[CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 27339863-Fluorophenylboronic acidHCID 155040625-bromo-1H,2H,3H-pyrrolo(2,3-b)pyridin-2-one

Product 1

HCID 469120855-(3-fluorophenyl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-oneYield 150.6%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

A mixture of 4 (16.63 g, 78.5 mmol), 3-fluorophenylboronic acid (16.47 g, 117.7 mmol), Pd(PPh3)2Cl2 (2.73 g, 6.60 mmol), LiCl (9.95 g, 0.23 mol), 1.0 M aqueous Na2CO3 solution (196 mL, 0.196 mol) in EtOH (470 mL)—toluene (470 mL) was refluxed overnight. More Pd(PPh3)2Cl2 (1.30 g, 3.14 mmol) was added and reflux was continued for 24 h. The mixture was cooled, and the organic layer was separated and washed with brine (100 mL). The washings were combined with the aqueous layer and extracted with AcOEt (4×400 mL). Combined extracts were washed with brine, added to the organic layer and dried with MgSO4. The solution was concentrated to dryness in vacuum to give 26.98 g of brown semisolid, which was triturated with ether:hexane=1:1 (2×500 mL). The residue was dried in vacuum to afford 5 (16.85 g, 94%) as tan solid, which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 3.66 (s, 2H), 7.08 (dddd, J=8.4, 8.2, 2.4, 0.9 Hz, 1H), 7.22 (ddd, J=10.0, 2.4, 1.7 Hz, 1H), 7.30 (ddd, J=8.1, 1.7, 0.9 Hz, 1H), 7.43 (ddd, J=8.2, 8.1, 6.0 Hz, 1H), 7.69 (s, 1H), 8.36 (d, J=2.1 Hz, 1H), 8.98 (bs, 1H).

Workup

  1. temperaturewas refluxed overnight
  2. temperaturereflux
  3. temperatureThe mixture was cooled
  4. customthe organic layer was separated
  5. washwashed with brine (100 mL)
  6. extractionextracted with AcOEt (4×400 mL)
  7. washCombined extracts were washed with brine
  8. additionadded to the organic layer
  9. dry with materialdried with MgSO4
  10. concentrationThe solution was concentrated to dryness in vacuum

Sources & evidence

ORD record
ord-6b265952ff7b4462b0879dd5dd74f5d8
Source dataset
uspto-grants-2009_05
Patent number
US07534800B2

Reaction notes

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