Dihydrocholesterol → 3beta-(Prop-2-ynyloxy)cholestanol

3β-cholestanol (1.23 g, 3.16 mmol) was completely dissolved in anhydrous toluene (7 mL, 0.45 M) at r.t. Powdered potassium t-butoxide (1.06 g, 9.49 mmol, 3 eq) was added in one portion. The mixture was stirred at r.t. for 3 h. A solution of propargyl bromide (80 wt % in toluene, 0.94 g, 6.32 mmol, 2 eq) was added. The mixture was stirred at r.t. for 3 days. The mixture was diluted with hexane (30 mL) and EtOAc (10 mL), washed with water (2×60 mL) and brine (60 mL). The aqueous phase was extracted once with EtOAc (20 mL). The combined organic phases were dried (Na2SO4), filtered and the filtrate was evaporated onto silica gel and purified by column chromatography (silica gel 2.5×24 cm, gradient elution with hexane 250 mL, hexane-EtOAc 125:5) to give the product as a yellow solid. Recrystallization from EtOAc (3 mL) gave off-white crystals (736 mg, 55%). 1H NMR (CDCl3, 400 MHz) δ 4.18 (d, 2H, J=2.2), 3.45 (m, 1H), 2.38 (t, 1H, J=2.2), 1.99-0.57 (m, 31H), 0.89 (d, 3H, J=6.6), 0.86 (d, 3H, J=6.6), 0.86 (d, 3H, J=6.6), 0.79 (s, 3H), 0.64 (s, 3H).

1. stirringThe mixture was stirred at r.t. for 3 days
2. washwashed with water (2×60 mL) and brine (60 mL)
3. extractionThe aqueous phase was extracted once with EtOAc (20 mL)
4. dry with materialThe combined organic phases were dried (Na2SO4)
5. filtrationfiltered
6. customthe filtrate was evaporated onto silica gel
7. custompurified by column chromatography (silica gel 2.5×24 cm, gradient elution with hexane 250 mL, hexane-EtOAc 125:5)

ORD record

ord-217acad05b48403ebec4ecfc19a402bd

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08828952B2