Water → (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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence