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

온도

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, 9 H), 1.45-1.48 (m, 1 H), 1.62-1.73 (m, 3 H), 1.78-1.82 (m, 2 H), 2.71 (s, 3 H), 2.78-2.81 (m, 2 H), 3.66 (s, 3 H), 4.99 (s, 1 H), 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 기록

ord-cff64896f6fa4c029aa093d89ae62bd0

출처 데이터셋

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09447116B2