Hydrochloric Acid → HCID 58074318, compound

Temperature

0 °C

1-(2-Chloro-phenyl)-ethanol (1.0 g, 6.39 mmol, 3.6 Eq) and Et3N (1.16 mL, 8.30 mmol, 4.7 Eq) were dissolved in anhydrous DCM (20 mL) and cooled to 0° C. under nitrogen. MsCl (645 μL, 8.30 mmol, 4.7 Eq) was added portionwise. After 3.5 hours, the reaction was poured into 1M HCl (20 mL) and the layers separated. The aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic extracts washed with brine (30 mL), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in dioxane (6 mL) and 1,2,3,4-tetrahydro-thieno[3,2-e][1,4]diazepin-5-one (300 mg, 1.78 mmol, 1.0 Eq) was added and the reaction heated at reflux overnight. The reaction was cooled to ambient temperature and the solvent removed in vacuo. The residue was purified by column chromatography (ISCO™ Companion©, 40 g column, 0 to 10% MeOH/DCM) to give the title compound as an off-white solid (178 mg, 0.06 mmol, 33%); 1H NMR (DMSO D6) 1.50 (3H, d), 2.92-2.99 (1H, m), 3.13 (1H, m), 3.20-3.25 (2H, m), 5.32 (1H, dd), 6.91 (1H, d), 7.25-7.35 (2H, m), 7.36-7.41 (2H, m), 7.58 (1H, d), 7.61-7.63 (1H, m); LC/MS M+1 (obs.) 307.0.

1. customthe layers separated
2. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
3. washthe combined organic extracts washed with brine (30 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated in vacuo
6. dissolutionThe residue was dissolved in dioxane (6 mL)
7. temperaturethe reaction heated
8. temperatureat reflux overnight
9. temperatureThe reaction was cooled to ambient temperature
10. customthe solvent removed in vacuo
11. customThe residue was purified by column chromatography (ISCO™ Companion©, 40 g column, 0 to 10% MeOH/DCM)

ORD record

ord-a76abb55417644d9a39fec5cd5bcdefe

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07838517B2