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

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).

1. customIn a dry 200 mL round-bottomed flask was
2. customto give a colorless solution
3. customThe resultant solution was quenched
4. additionby slowly adding 100 mL of NaHCO3 solution
5. extractionextracting with EtOAc (3×100 mL)
6. washThe combined organic phase was washed with brine (1×100 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in a 500 mL round bottomed flask
10. temperatureto reflux for 2 h
11. temperatureThe solution was cooled to room temperature
12. customevaporated to dryness
13. stirringto stir overnight
14. extractionextracted with ethyl acetate (3×100 mL)
15. washwashed with brine (1×50 mL)
16. dry with materialdried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated
19. customThe resultant wax was purified via column chromatography on a 40 g Biotage SNAP column
20. washeluting with a 0-50% gradient over 1 L
21. customevaporated to dryness

ORD record

ord-08a3f530cec6410dbdabfe99a339c236

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012225B2