(1S)-2-[benzyl-[(2S)-2-[(2S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl]amino]-1-[(2R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]ethanol

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (±)[R*,S*,S*,S*]-α,α′-[(phenylmethyl)imino-bis (methylene)] bis [6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] (5.0 g; 0.0101 mol) was dissolved in methanol (343.9 g). Ammonium formate (4.8 g; 0.0761 mol) was added to the reaction mixture followed by catalytic Palladium on carbon 5 wt. % wet (contains ˜50% water) (0.5 g). The reaction mixture was heated at reflux (about 65° C.) under stirring for about 11 hours then cooled to 45° C. filtered on a celite pad, washing with methanol, and finally concentrated under vacuum. The crude residue (6.2 g) was diluted with 2-butanol (65.2 g) then a solution of aq. 30% sodium hydroxide (2.0 g) and water (29.8 g) was added under stirring. The resulting suspension was heated to 70±2° C. until complete dissolution obtaining a clear two-phase mixture. The aqueous layer was separated and the resulting organic phase was washed with aq. sodium hydrogen carbonate (1.7 g dissolved in 22.6 g of water) and then with water (2×21.5 g). Toluene (5.0 g) was also added to improve the aqueous-organic separation. The organic phase was concentrated two-times under reduced pressure while adding fresh 2-butanol (total 32.9 g) to the resulting residues. The final organic solution (about 60 ml) was further diluted with 2-butanol (9.5 g) heated to 85-90° C. until complete dissolution and then gradually cooled to 20° C. obtaining the product precipitation. The solid was isolated by filtration, washing with 2-butanol (3×2.7 g), and dried under vacuum at 60° C. to give the title compound as a white solid (3.5 g, 96.6% w/w assay (HPLC); 82.6% molar yield). Purity Profile (HPLC): Sum of Impurities=0.284% w/w; Max Single Impurity (“de-F” Nebivolol)=0.196% w/w. The reaction mixture was heated then cooled to 45° C. filtered on a celite pad washing with methanol finally concentrated under vacuum The crude residue (6.2 g) was diluted with 2-butanol (65.2 g) a solution of aq. 30% sodium hydroxide (2.0 g) and water (29.8 g) was added under stirring The resulting suspension was heated to 70±2° C. until complete dissolution obtaining a clear two-phase mixture The aqueous layer was separated the resulting organic phase was washed with aq. sodium hydrogen carbonate (1.7 g dissolved in 22.6 g of water) Toluene (5.0 g) was also added the aqueous-organic separation The organic phase was concentrated two-times under reduced pressure while adding fresh 2-butanol (total 32.9 g) to the resulting residues The final organic solution (about 60 ml) was further diluted with 2-butanol (9.5 g) heated to 85-90° C. until complete dissolution gradually cooled to 20° C. obtaining the product precipitation The solid was isolated by filtration washing with 2-butanol (3×2.7 g) dried under vacuum at 60° C.