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

温度

100 °C

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, 100 mg, 212 μmol) in dioxane (2 mL) was added 4-chlorobenzene boronic acid (66 mg, 422 μmol), ethyl-di-isopropyl-amine (120 μL, 636 μmol), water (500 μL) and palladium tetrakis(triphenylphosphine) (25 mg, 20 μmol). The reaction mixture was degassed and stirred at 100° C. in a sealed tube. The reaction was cooled to room temperature and diluted with ethyl acetate (10 mL). The mixture was passed through a pad of Celite. The organic filtrate was washed with water (10 mL) and brine (10 mL), dried over MgSO4 and concentrated in vacuo to yield the crude product. The residue was purified by flash chromatography eluting with ethyl acetate in heptane (0-6%) to give the title compound as a white semi-solid, 60 mg, in a 62% yield. 1H NMR (400 MHz, CDCl3) δ ppm 0.97 (s, 9H), 1.45-1.48 (m, 1H), 1.62-1.73 (m, 3H), 1.78-1.82 (m, 2H), 2.71 (s, 3H), 2.78-2.81 (m, 2H), 3.66 (s, 3H), 4.99 (s, 1H), 7.18-7.21 (m, 1H), 7.39-7.42 (m, 3H).

1. customThe reaction mixture was degassed
2. temperatureThe reaction was cooled to room temperature
3. additiondiluted with ethyl acetate (10 mL)
4. washThe organic filtrate was washed with water (10 mL) and brine (10 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customto yield the crude product
8. customThe residue was purified by flash chromatography
9. washeluting with ethyl acetate in heptane (0-6%)

ORDレコード

ord-f62cb6ef294747458bee54b24f585515

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08809363B2