Isopropanol → 1-((3R)-6,8-Difluoro-3,4-dihydro-2H-1-benzopyran-3-yl)-1,3-dihydro-5-(2-((phenylmethyl)amino)ethyl)-2H-imidazole-2-thione

Temperature

22.5 °C

(R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (12 g, 29.9 mmol) was dissolved with heating to reflux in Tetrahydrofuran (300 ml), the solution was cooled to 5-10° C., Water (510 ml) was added slowly (approx 10 min) with stirring. The mixture was stirred for 1 h, solid was collected, washed with water, dried to give 11.73 g of product, by HPLC 1% of (R)-5-(2-Aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione hydrochloride and 1% of less polar impurity. The product was dissolved in Tetrahydrofuran (300 ml) with heating to reflux, 2-Propanol (150 ml) was added, the solution was concentrated to approx 100 ml (crystallisation occurred), stirred in ice for 1.5 h. Solid was collected, washed with 2-propanol, dried to give 11.2 g of product, by HPLC 0.8% of (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione hydrochloride and 0.5% of less polar impurity. The product was dissolved in Tetrahydrofuran (300 ml) with heating to reflux, 2-Propanol (150 ml) was added, the solution was concentrated to approx 100 ml (crystallisation occurred), stirred at 20-25° C. for 1 h. Solid was collected, washed with 2-propanol, dried to give (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione (10.22 g, 25.5 mmol, 85% yield).,

1. temperaturewith heating
2. temperatureto reflux
3. concentrationthe solution was concentrated to approx 100 ml (crystallisation occurred)
4. customSolid was collected
5. washwashed with 2-propanol
6. customdried

ORD record

ord-b8ede0aff87e43ebbff1ea91a1a5e9b9

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08865913B2