Hydrochloric Acid → 2H-1-Benzopyran-2-methanol, alpha,alpha'-(iminobis(methylene))bis(6-fluoro-3,4-dihydro-, hydrochloride (1:1), (alphaR,alpha'R,2R,2'S)-rel-

Temperatur

70 °C

(±)[R*,S*,S*,S*]-α,α′-[imino-bis (methylene)] bis [6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] (3.106 g; 96.6% w/w; 0.00740 mol) was dissolved in a mixture of 2-butanol (33.1 g) and water (2.0 g). Aq. conc. (about 31%) hydrochloric acid (1.1 g; 0.00903 mol) was added to the solution under stirring at 70±2° C. The resulting mixture was heated at 70±2° C. for 2 hours, then cooled to 20±2° C. over 2 hours and maintained at this temperature for further 2 hours obtaining the product precipitation. The solid was isolated by filtration, washing with 2-butanol (2×2 g), and dried under vacuum at 60° C. to give the title compound as a white solid (3.1 g, 98.3% w/w assay (HPLC); 93.2% molar yield). Purity Profile (HPLC): Sum of Impurities=0.224% w/w; Max Single Impurity (“de-F” Nebivolol)=0.178% w/w.

1. temperatureThe resulting mixture was heated at 70±2° C. for 2 hours
2. temperaturecooled to 20±2° C. over 2 hours
3. temperaturemaintained at this temperature for further 2 hours
4. customobtaining
5. customthe product precipitation
6. customThe solid was isolated by filtration
7. washwashing with 2-butanol (2×2 g)
8. customdried under vacuum at 60° C.

ORD-Eintrag

ord-c6eeb6422bb649d5ab8e30cc7ad16b56

Quelldatensatz

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08927742B2