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

Temperature

30 °C

To a solution of (2S)-tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetic acid (Preparation 15, 1.0 g, 2.178 mmol) in dichloromethane (34 mL) was added [(benzotriazol-1-yloxy)-dimethylamino-methylene]dimethyl-ammonium hexafluoro phosphate (1.24 g, 3.266 mmol) and ethyl-di-isopropyl-amine (600 μL, 3.266 mmol) and the resulting reaction mixture was stirred at 30° C. for 2 hours. Methanol (17 mL) was added and the reaction mixture was stirred at 30° C. for 18 hours. The reaction was cooled to room temperature and diluted with dichloromethane (50 mL). The solution was washed with a saturated aqueous solution of sodium hydrogen carbonate (50 mL), water (50 mL) and brine (50 mL). The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography eluting with 5% ethyl acetate in heptane to give the title compound as a white solid, 963 mg, in a 93% yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.22 (s, 9H), 1.85-1.88 (m, 4H), 2.65 (s, 3H), 2.82-2.86 (m, 2H), 3.23-3.26 (m, 2H), 3.68 (s, 3H), 5.94 (s, 1H).

1. customthe resulting reaction mixture
2. stirringthe reaction mixture was stirred at 30° C. for 18 hours
3. temperatureThe reaction was cooled to room temperature
4. washThe solution was washed with a saturated aqueous solution of sodium hydrogen carbonate (50 mL), water (50 mL) and brine (50 mL)
5. dry with materialThe organic layer was dried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe residue was purified by flash chromatography
8. washeluting with 5% ethyl acetate in heptane

ORD record

ord-296ac192b11c40d3933fc09c17053e99

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809363B2