Reacción #92245

Ecuación de reacción

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

sodium hydrogen carbonate

water

(S)-methyl 2-(tert-butoxy)-2-(4-iodo-2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate

→

title compound

Rendimiento 67.0%

(S)-methyl 2-(4-(4-aminophenyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridin-3-yl)-2-(tert-butoxy)acetate

Rendimiento 67.0%

Disolventes

N,N-dimethylacetamide

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction mixture was degassed with argon for 2 minutes
2. 2
   Otrothe vessel was sealed
3. 3
   TemperaturaThe reaction mixture was cooled to room temperature
4. 4
   Otropartitioned between dichloromethane (30 mL) and water (30 mL)
5. 5
   OtroThe layers were separated
6. 6
   Secadothe organic layer was dried (MgSO4)
7. 7
   Concentraciónconcentrated in vacuo
8. 8
   Otroto yield the crude product as a brown gum
9. 9
   OtroThe residue was purified by flash column chromatography on silica eluting with ethyl acetate in heptane (25%)

Procedimiento

4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (140 mg, 0.63 mmol), sodium hydrogen carbonate (178 mg, 2.1 mmol) and water (200 μL) were added to a stirred solution of (S)-methyl 2-(tert-butoxy)-2-(4-iodo-2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate (200 mg, 0.42 mmol) in N,N-dimethylacetamide (4 mL) in a reaction tube. The reaction mixture was degassed with argon for 2 minutes, then bis(tri-tert-butylphosphine)palladium(0) (22 mg, 42 μmol) was added and the vessel was sealed and heated at 100° C. for 16 hours. The reaction mixture was cooled to room temperature and partitioned between dichloromethane (30 mL) and water (30 mL). The layers were separated and the organic layer was dried (MgSO4) and concentrated in vacuo to yield the crude product as a brown gum. The residue was purified by flash column chromatography on silica eluting with ethyl acetate in heptane (25%) to give the title compound (114 mg, 67%) as a white foam. 1H NMR (400 MHz, CDCl3) δ 0.97 (s, 9H), 1.95-1.30 (m, 6H), 2.68 (s, 3H), 2.85-2.77 (m, 2H), 3.65 (s, 3H), 3.80 (brs, 2H), 5.19 (s, 1H), 6.75-6.68 (m, 2H), 6.99 (d, 1H), 7.19 (d, 1H).

Fuente