Hydrochloric Acid → 12-(Cholest-5-en-3beta-oxy)-3-hydroxydodecanal

Participants

Reaction Steps

In a dry 200 mL round-bottomed flask was 10-(Cholest-5-en-3β-oxy)decanal (2.65 g, 4.90 mmol) dissolved in THF (10 ml), under argon to give a colorless solution. A 0.5 M THF solution of ((1,3-dioxolan-2-yl)methyl)magnesium bromide (9.80 ml, 4.90 mmol) was added dropwise, and the resulting solution was allowed to stir for 4 h at room temperature. The resultant solution was quenched by slowly adding 100 mL of NaHCO3 solution and extracting with EtOAc (3×100 mL). The combined organic phase was washed with brine (1×100 mL), dried over sodium sulfate, filtered and concentrated in a 500 mL round bottomed flask. Trimethyl orthoformate (10.83 ml, 98 mmol), PPTS (0.246 g, 0.980 mmol) and methanol (10 ml) were added to the flask and the contents brought to reflux for 2 h. The solution was cooled to room temperature and evaporated to dryness. The residue was then taken up in Acetone (20 ml) and 1.0N HYDROCHLORIC ACID (4.90 ml, 4.90 mmol) and allowed to stir overnight. The reaction mixture was diluted to 200 mL with water and extracted with ethyl acetate (3×100 mL). The organic phase was combined, washed with brine (1×50 mL), dried over Na2SO4, filtered and concentrated. The resultant wax was purified via column chromatography on a 40 g Biotage SNAP column eluting with a 0-50% gradient over 1 L. The pure fractions were combined and evaporated to dryness to give 12-(Cholest-5-en-3β-oxy)-3-hydroxydodecanal (1.97 g, 3.37 mmol, 68.7% yield) as a colorless wax. 1H NMR (300 MHz, CDCl3) δ0.69 (3H, s); 0.85-1.74 (49H, m); 1.75-2.13 (7H, m); 2.14-2.28 (1H, m); 2.33-2.44 (1H, m); 3.14 (1H, tt, J=11.2, 4.4 Hz); 3.46 (2H, t, J=6.8 Hz); 3.93-4.10 (1H, m); 5.36 (1H, d, J=5.2 Hz); 5.42-5.55 (1H, m); 9.78 (1H, s).

Provenance & Evidence