Toluene → 1-(4-Bromopyridin-2-yl)cyclopropanecarbonitrile

HRID 2370370Notes

Reaction equation

HRID 2370370 reaction equation
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Br:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14](F)[CH:13]=1.[CH:19]1([C:22]#[N:23])[CH2:21][CH2:20]1.C1(C)C=CC=CC=1>O>[Br:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14]([C:19]2([C:22]#[N:23])[CH2:21][CH2:20]2)[CH:13]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 79637CyclopropanecarbonitrileHCID 2733832Lithium HexamethyldisilazideHCID 27628514-Bromo-2-fluoropyridine

Product 1

HCID 574170931-(4-Bromopyridin-2-yl)cyclopropanecarbonitrileYield 48.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

LiHMDS (1M in toluene, 17.6 mL, 17.6 mmol, 3.1 eq) is added dropwise to a cold (−5° C.) mixture of 4-bromo-2-fluoro-pyridine [Marsais, F. et al, Journal of Organic Chemistry, (1992), 57, 565-573] (1 g, 5.7 mmol), cyclopropanecarbonitrile (1.25 mL, 17 mmol, 3 eq), 4 Å molecular sieves and toluene (20 mL). The reaction mixture is allowed to warm to rt, stirred for 16 h, poured into H2O and filtered. The filtrate is diluted with EtOAc/H2O and extracted with EtOAc. The organic phase is washed with H2O and brine, dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel column chromatography (Hex/EtOAc, 9:1), to afford 620 mg of the title compound as a white solid: ESI-MS: 223.1/225.1 [M+H]+; tR=4.22 min (System 1); TLC: Rf=0.25 (Hex/EtOAc, 9:1).

Workup

  1. filtrationfiltered
  2. additionThe filtrate is diluted with EtOAc/H2O
  3. extractionextracted with EtOAc
  4. washThe organic phase is washed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue is purified by silica gel column chromatography (Hex/EtOAc, 9:1)

Sources & evidence

ORD record
ord-bfb5d875afbd435a93e573a3f6472521
Source dataset
uspto-grants-2014_04
Patent number
US08710085B2

Reaction notes

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