1,2:5,6-Bis-O-(1-methylethylidene)-D-mannitol

The unsaturated ester 20 d-mannitol (19) (20 g, 0.11 mol) was added to a stirred solution of molten zinc chloride (30 g, 0.22 mol) in dry acetone (200 mL). Stirring continued until the d-mannitol was completely dissolved (22 hours). The reaction mixture was then poured into a stirred and cooled aqueous solution of K₂CO₃ (30 g, 0.22 mol) (320 mL). The precipitate was removed by filtration and thoroughly washed with DCM (200 mL). The aqueous filtrate was evaporated to remove acetone, and the extract was extracted with DCM (3 x 200 mL). The organic washes and extract were washed with cold water (100 mL), dried with MgSO₄, evaporated to a solid residue, and recrystallized to give diacetone-D-mannitol 19A as a white needle (18.3 g, 60%).

A solution of acetal 6a (210 mg, 0.57 mmol) in pyrrolidine (8 mL) was heated to 90°C for 48 hours. After solvent removal, the residue was purified by “rapid” column chromatography (hexane-EtOAc) to give 1,2:5,6-Bis-O-(1-methylethylidene)-D-mannitol (129 mg, 91%, 94%).

White Solid

Nebivolol intermediate.

Although quite soluble in H2O, it gives a purer product when crystallised from this solvent, forming needles [Baer J Am Chem Soc 67 338 1945, NMR: Curtis et al. J Chem Soc, Perkin Trans 1 1756 1977]. [Beilstein 19/11 V 589.]