Chlorotrimethylsilane → HCID 71659933, compound

(C6H6) (10.1 mg, 0.02 mmol, 0.05 eq.) and the phosphoramidite ligand (21.6 mg, 0.040 mmol, 0.10 eq.) were dissolved in Et2O (2.0 mL) under an argon atmosphere and allowed to stir for 1 h at room temperature. In another flask, Cp2ZrHCl (206.0 mg, 0.80 mmol, 2.0 eq.) was added to a stirred, room temperature, solution of 1-hexene (0.13 mL, 1.0 mmol, 2.5 eq.) in CH2Cl2 (0.40 mL) under an argon atmosphere. After stirring for 40 min, the resulting clear yellow solution was transferred via syringe over about 1 min to the stirred solution containing the copper and ligand under an argon atmosphere. The resulting dark mixture was allowed to stir for an additional 10 min before 1,4-androstadiene-3,17-dione (114.0 mg, 0.40 mmol, 1.0 eq.) and TMSCl (0.26 mL, 2.00 mmol, 5.0 eq.) were added sequentially dropwise via syringe. Stirring at room temperature was continued arbitrarily for 15 h before the reaction was quenched by the addition of Et2O (ca 3 mL) and NH4Cl (1 M aq., ca 1.5 mL). The mixture was partitioned between the aqueous and Et2O layers and the former phase was extracted with Et2O (3×10 mL). The combined organic phase was washed with NaHCO3 (sat. aq., ca 10 mL), dried (Na2SO4), filtered and concentrated in vacuo to give an oil. Flash column chromatography of the yellow residue (5:30:65 EtOAc/DCM/petrol; SiO2) gave major diastereomer (1) (+)-1α-hexyl-4-androstene-3,17-dione (75 mg, 0.20 mmol, 50%) and minor diastereomer (1a) (+)-1α-hexyl-4-androstene-3,17-dione (24 mg, 0.064 mmol, 16%). Diastereomeric ratio (3.6:1) was determined by integration of 1H NMR spectra.

1. stirringAfter stirring for 40 min
2. waitthe resulting clear yellow solution was transferred via syringe over about 1 min to the stirred solution
3. additionwere added sequentially dropwise via syringe
4. stirringStirring at room temperature
5. waitwas continued arbitrarily for 15 h before the reaction
6. customwas quenched by the addition of Et2O (ca 3 mL) and NH4Cl (1 M aq., ca 1.5 mL)
7. customThe mixture was partitioned between the aqueous and Et2O layers
8. extractionthe former phase was extracted with Et2O (3×10 mL)
9. washThe combined organic phase was washed with NaHCO3 (sat. aq., ca 10 mL)
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customto give an oil

ORD record

ord-7d94bd575ce641d4981181420bf80b40

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09090545B2