p-Toluenesulphonyl cyanide → 7-Chlorothieno[3,2-B]pyridine-2-carbonitrile

HRID 1063170Notes

Reaction equation

HRID 1063170 reaction equation
C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[CH:14][S:15][C:8]=12.S([C:26]#[N:27])(C1C=CC(C)=CC=1)(=O)=O>C1COCC1>[Cl:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:26]#[N:27])[S:15][C:8]=12

Participants

5

Reactant 3

HCID 87946p-Toluenesulphonyl cyanideHCID 112752517-Chlorothieno[3,2-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 222786367-Chlorothieno[3,2-B]pyridine-2-carbonitrileYield 32%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

n-Butyllithium (2.2 mmol, 0.88 mL) was added dropwise to a solution of 7-chloro-thieno[3,2-b]pyridine (0.250 g, 1.48 mmol) in THF (10 mL) at −78° C. while the internal temperature was kept below −70° C. After 1 h TsCN (0.804 mg, 4.44 mmol) was added. After 3 h the reaction was quenched with distilled water (10 mL), warmed to rt, and the layers were separated. The aqueous layer was further extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried (Na2SO4), then concentrated under reduced pressure. Purification by flash chromatography using a Biotage 40 S column eluting with hexane/ethyl acetate (7/3) afforded the title compound as a white solid (92 mg, 32%). MS: 195/197 (MH+); HPLC Rf: 4.89 min; HPLC purity: 85%.

Workup

  1. customwas kept below −70° C
  2. customAfter 3 h the reaction was quenched with distilled water (10 mL)
  3. customthe layers were separated
  4. extractionThe aqueous layer was further extracted with ethyl acetate (3×10 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash chromatography
  8. washeluting with hexane/ethyl acetate (7/3)

Sources & evidence

ORD record
ord-e457838eb52640d5b99eb23e01955ecf
Source dataset
uspto-grants-2005_11
Patent number
US06964961B2

Reaction notes

Loading…