Carbon tetrabromide → 5-Bromo-4-fluoro-1-[tris(1-methylethyl)silyl]-1H-pyrrolo[2,3-b]pyridine

HRID 1034658Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:9]=[CH:10][C:3]=12.C([Li])(CC)C.[Br:26]C(Br)(Br)Br>C1COCC1>[Br:26][C:7]1[C:2]([F:1])=[C:3]2[CH:10]=[CH:9][N:8]([Si:11]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[CH:12]([CH3:13])[CH3:14])[C:4]2=[N:5][CH:6]=1

Participants

Conditions

Temperature: -78 °C

Procedure

4-Fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (28.0 g, 95.7 mmol) in THF (600 mL) at −78° C. was treated dropwise with sec-butyllithium (150 mL, 211 mmol; 1.4M in cyclohexane). The reaction was stirred at −78° C. for 30 minutes. Perbromomethane (79.4 g, 239 mmol) in THF (100 mL) was then added dropwise. The reaction was stirred at −78° C. for 1 hour and then quenched with saturated aqueous NH4Cl. The aqueous phase was extracted with hexanes. The combined organic phases were dried (MgSO4) and concentrated in vacuo. The oil obtained was purified by flash chromatography on silica gel eluting with hexanes to provide 5-bromo-4-fluoro-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine (30 g, 84% yield) as an oil, which solidified upon standing. 1H NMR (400 MHz, CDCl3) δ 8.28 (d, 1H), 7.26 (s, 1H), 6.62 (d, 1H), 1.86-1.78 (m, 3H), 1.11 (d, 18H).

Workup

stirringThe reaction was stirred at −78° C. for 1 hour
customquenched with saturated aqueous NH4Cl
extractionThe aqueous phase was extracted with hexanes
dry with materialThe combined organic phases were dried (MgSO4)
concentrationconcentrated in vacuo
customThe oil obtained
customwas purified by flash chromatography on silica gel eluting with hexanes

Sources & evidence

ORD record: ord-d0f9ed5e4f7240138aef2b8c41514ac2
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08545897B2

Reaction notes

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