Boron trifluoride etherate → 5-Bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 2046906Notes

Reaction equation

HRID 2046906 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])O)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.B(F)(F)F.[CH3:26]COCC.[Zn](C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])[CH3:26])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 67004517(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)(2,6-dichloro-3-fluorophenyl)methanolHCID 178477796HCID 178477796, compound

Product 1

HCID 584314405-Bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-(2,6-dichloro-3-fluorophenyl)methanol (5.05 g, 12.9 mmol) was dissolved in anhydrous THF (100 mL). To this solution was added BF3.OEt2 (10.66 mL, 6.5 eq.) at −78° C. The resulting solution was stirred for 10 min at the same temp before a solution of ZnMe2 (35.60 mL, 5.5 eq., 2 N in toluene) was added. The resulting mixture was allowed to warm up to rt in 1 h. The solution was then stirred at 65° C. for 3.5 h. Reaction was monitored by LC-MS. After achieving >95% conversion, the reaction was allowed to cool down to rt. Then it was further cooled down to −78° C. and quenched by adding sat. aq. NH4Cl solution (10 mL). The mixture was slowly warmed up to rt. Solvents were removed under reduced pressure. To the residue was added aq. NaHCO3 solution and the mixture was then extracted with CHCl3 (100 mL×4). The organic extracts were combined, dried (Na2SO4), and concentrated in vacuo to give a crude residue which was purified by flash chromatography (eluent: 10% ethyl acetate in hexane). 1H NMR (400 MHz. DMSO-d6): δ=11.85 (br. s., 1H), 8.21 (d, J=2.0 Hz, 1H), 7.49-7.59 (m, 2H), 7.41 (dd, J=8.8, 8.6 Hz, 1H), 7.30 (d, J=2.0 Hz, 1H), 5.11 (q, J=7.3 Hz, 1H), 1.80 (d, J=7.3 Hz, 3H); 13C NMR (100.6 MHz, DMSO-d6): δ 156.74 (JCF=247.4 Hz), 146.91, 142.24, 141.02, 129.37, 127.56, 125.98, 121.73 (JCF=19.8 Hz), 120.18, 115.98 (JCF=23.4 Hz), 113.62, 109.99, 33.53, 15.94. MS (ES+): m/z=386.93, 388.91, 390.89 [MH+]. HPLC: tR=4.17 min (ZQ3, polar—5 min).

Workup

  1. additionwas added
  2. customReaction
  3. temperatureto cool down to rt
  4. temperatureThen it was further cooled down to −78° C.
  5. customquenched
  6. additionby adding sat. aq. NH4Cl solution (10 mL)
  7. temperatureThe mixture was slowly warmed up to rt
  8. customSolvents were removed under reduced pressure
  9. additionTo the residue was added aq. NaHCO3 solution
  10. extractionthe mixture was then extracted with CHCl3 (100 mL×4)
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-69d2080a72544f0e8aaa866db50a1987
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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