Propargyl bromide → Pregnane-3,20-dione

Temperature

-75 °C

A solution of 2-(2-propynyl)-2H-1,2,3-triazole (prepared by the reaction of triazole with propargyl bromide) (35 mg, 0.33 mmol) in dry THF (10 mL) was treated with n-BuLi (2.5M in THF, 0.33 mmol, 0.15 mL) at -70° C. After stirring the mixture at -75° C. for 0.5 hr, a solution of 5β-pregnan-3,20-dione, cyclic 20-(1,2-ethanediyl acetal) (60 mg, 0.16 mmol) in THF (10 mL) was added and the mixture was stirred at -78° C. for 1 hr. The cooling bath was removed and the mixture was quenched with NH4Cl solution (1 mL). The solvent was removed and the residue was then dissolved in acetone (25 mL). After adding 2N HCl (2 mL) the solution was stirred at rt for 30 min. Sat. NaHCO3 soln. was added to neutralize the acid. The solvents were removed and the residue was extracted with EtOAc. The organic layer was washed with water, and brine. After drying over anhyd. MgSO4 the solution was filtered and evaporated to yield the crude product. This crude product was then dissolved in a small amount of CH2Cl2 and poured on a column of silica gel. Elution with toluene:acetone mixture (85:15) gave pregnan-3,20-dione (20 mg) as a first fraction. Further elution with the same solvent yielded 3α-hydroxy-3β-[3-(2'H-1,2,3-triazol-2'-yl)-1-propynyl]-5β-pregnan-20-one (20 mg) as a colorless solid; mp 139-140° C.; TLC Rf (hexane:acetone 4:1)=0.17.

1. stirringthe mixture was stirred at -78° C. for 1 hr
2. customThe cooling bath was removed
3. customthe mixture was quenched with NH4Cl solution (1 mL)
4. customThe solvent was removed
5. dissolutionthe residue was then dissolved in acetone (25 mL)
6. additionAfter adding 2N HCl (2 mL) the solution
7. stirringwas stirred at rt for 30 min
8. additionwas added
9. customThe solvents were removed
10. extractionthe residue was extracted with EtOAc
11. washThe organic layer was washed with water, and brine
12. customAfter drying over anhyd
13. filtrationMgSO4 the solution was filtered
14. customevaporated
15. customto yield the crude product
16. additionpoured on a column of silica gel
17. washElution with toluene

ORD record

ord-6392f123faa0441ca29e7cd14a85806d

Source dataset

uspto-grants-1999_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05939545