Reaktion #1568892

Reaktionsgleichung

6-Chloro-5-ethyl-2-methoxynicotinate

KOAc

2-Bromo-5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrole

K2CO3

→

Methyl 6-(5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrol-2-yl)-5-ethyl-2-methoxynicotinate

Ausbeute 50.1%

Lösungsmittel

H2O

H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedried vial
2. 2
   workup.ADDITIONwas added
3. 3
   Temperaturthen was cooled to room temperature
4. 4
   Sonstigereaction
5. 5
   Temperaturmixture was heated at 100° C. for 2 h
6. 6
   TemperaturMixture was then cooled to room temperature
7. 7
   Extraktionwas extracted with DCM (3×20 mL)
8. 8
   WaschenCombined organics were washed with NaCl (aqueous saturated, 15 mL)
9. 9
   Trocknendried over Na2SO4
10. 10
    SonstigeAfter concentration of the solvent the residue was purified by column chromatography (EtOAc/hexanes, 0-15% gradient)

Vorschrift

6-Chloro-5-ethyl-2-methoxynicotinate (0.575 g, 2.50 mmol), bis(pinacolato) diborate (0.800 g, 315 mmol), Pd(dppf)Cl2 (73.0 mg, 0.1 mmol, 4 mol %), and KOAc (0.750 g, 7.64 mmol) were mixed together in a heat-gun dried vial. The vial was vacuumed and backfilled with argon before dioxane (10 mL) was added. Mixture was heated at 100° C. overnight then was cooled to room temperature. 2-Bromo-5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrole (0.900 g, 2.50 mmol), fresh Pd(dppf)Cl2 (73.0 mg, 0.1 mmol, 4 mol %), K2CO3 (1.05 g, 7.60 mmol) and H2O (2.50 mL) were added and reaction vial was resealed under argon and mixture was heated at 100° C. for 2 h. Mixture was then cooled to room temperature, diluted with H2O (15 mL) and product was extracted with DCM (3×20 mL). Combined organics were washed with NaCl (aqueous saturated, 15 mL) and dried over Na2SO4. After concentration of the solvent the residue was purified by column chromatography (EtOAc/hexanes, 0-15% gradient). Methyl 6-(5-((tert-butyldimethylsilyloxy)methyl)-6-methyl-6H-thieno[2,3-b]pyrrol-2-yl)-5-ethyl-2-methoxynicotinate (0.594 g) was obtained as oil and was taken directly into the next step.

Quelle