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-936234189d5849419a25c589da4730f8

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399458B2