Sodium hydride → 2-Fluoro-3-{3-fluoro-1-[tris(1-methylethyl)silyl]-1H-pyrrol-2-yl}pyridine

HRID 2047899Notes

Reaction equation

HRID 2047899 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([C:10]2[NH:11][CH:12]=[CH:13][C:14]=2[F:15])=[CH:8][CH:7]=[CH:6][N:5]=1.C1OCCOCCOCCOCCOC1.FC(F)(F)S(O[Si:37]([CH:44]([CH3:46])[CH3:45])([CH:41]([CH3:43])[CH3:42])[CH:38]([CH3:40])[CH3:39])(=O)=O>O1CCCC1>[F:3][C:4]1[C:9]([C:10]2[N:11]([Si:37]([CH:44]([CH3:46])[CH3:45])([CH:41]([CH3:43])[CH3:42])[CH:38]([CH3:40])[CH3:39])[CH:12]=[CH:13][C:14]=2[F:15])=[CH:8][CH:7]=[CH:6][N:5]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 3633615-Crown-5HCID 2724529Triisopropylsilyl trifluoromethanesulfonateHCID 583498262-fluoro-3-(3-fluoro-1H-pyrrol-2-yl)pyridine

Product 1

HCID 671787532-Fluoro-3-{3-fluoro-1-[tris(1-methylethyl)silyl]-1H-pyrrol-2-yl}pyridineYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (3.32 g) in tetrahydrofuran (70 mL) was added dropwise a solution of 2-fluoro-3-(3-fluoro-1H-pyrrol-2-yl)pyridine (5.98 g) in tetrahydrofuran (30 mL) under ice-cooling and the mixture was stirred for 30 min. 15-Crown-5 (18.3 g) and tris(1-methylethyl)silyl trifluoromethanesulfonate (25.4 g) were added, and the mixture was stirred for 1 hr. The solvent was evaporated to a half volume under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The separated aqueous layer was extracted again with ethyl acetate. Combined organic layers were washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane→hexane-ethyl acetate=19:1) to give the title compound as a pale-yellow oil (yield 10.9 g, 98%).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 1 hr
  3. customThe solvent was evaporated to a half volume under reduced pressure, water
  4. additionwas added
  5. extractionthe mixture was extracted with ethyl acetate
  6. extractionThe separated aqueous layer was extracted again with ethyl acetate
  7. washCombined organic layers were washed with saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by basic silica gel column chromatography (eluent: hexane→hexane-ethyl acetate=19:1)

Sources & evidence

ORD record
ord-6551cb9d78934828a762367f56795df5
Source dataset
uspto-grants-2013_11
Patent number
US08592597B2

Reaction notes

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