Water → Methyl (2S)-tert-butoxy[4-(4-chloro-2-hydroxyphenyl)-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl]acetate

Participants

Reaction Conditions

Reaction Steps

To a solution of Methyl (2S)-tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetate (Preparation 16, 200 mg, 422 μmol) in dioxane (4 mL) was added (4-chloro-2-hydroxyphenyl) boronic acid (Preparation 17, 191 mg, 761 μmol), Dichloro [1,1′ bis(di-tert-butylphosphino)]ferrocene palladium (II)™ (Pd-118) (Johnson-Matthey, 27 mg, 10 mol %, 42.2 μmol), potassium phosphate (180 mg, 844 μmol) and water (1 mL). The resulting mixture was stirred at 105° C. in a sealed tube for 18 hours. A further portion of Pd-118 (10 mg, 3.7 mol %, 15.6 μmol) was added and the mixture stirred at 105° C. for 72 hours. The reaction mixture was cooled to room temperature and filtered through a short pad of silica, washing with ethyl acetate. The solvent was removed in vacuo. The crude product was purified by column chromatography eluting with ethyl acetate/heptane (0-10%) to yield the title compound as a brown solid, 37.5 mg, in a 19% yield. Material obtained was a mixture of atropisomers, in a ˜2:1 ratio and was carried on to hydrolysis step 2 without further purification.

Provenance & Evidence