Reacción #1691

Ecuación de reacción

dimethylformamide

n-butyllithium

citric acid

2-thiophenecarbonitrile

dry ice acetone

diisopropylamine

→

2-cyano-5-formyl-thiophene

Rendimiento 84.0%

Disolventes

THF

water

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroTo a flame-dried 3 neck 1 L round bottom flask
2. 2
   workup.ADDITIONwas added via syringe
3. 3
   workup.STIRRINGto stir for 2 h at -78° C.
4. 4
   OtroVolatile solvents were removed in vacuo
5. 5
   Otrothe residue was partitioned between diethyl ether and brine (200 mL each)
6. 6
   OtroLayers were separated
7. 7
   Lavadothe aqueous phase was washed once with diethyl ether
8. 8
   LavadoThe combined organic phase was washed once with brine
9. 9
   Secadodried (MgSO4)
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated in vacuo
12. 12
    Otroto give a yellow solid which
13. 13
    Otrowas purified by silica gel chromatography
14. 14
    workup.ADDITIONFractions containing pure product
15. 15
    Concentraciónconcentrated in vacuo

Procedimiento

To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50% ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84%) of 2-cyano-5-formyl-thiophene.

Fuente