Tetrahydrofuran → Allopregnanolone

Participants

Reaction Conditions

Reaction Steps

The reaction was carried out under a dry N2 atmosphere. Potassium ⟦trisamylborohydride⟧ trisiamylborohydride solution (KS-⟦Selectide⟧Selectride) in THF (6 cc, 5.83 mmol) was introduced into a three neck round bottom flask and cooled to 0° C. 5α-Pregnan-3,20-dione (1.58 g, 5 mmol) dissolved in 10 reducing agent. The resulting mixture was stirred vigorously for 2 hours at 0° C. and then allowed to equilibrate to room temperature for 1 hour. The reaction was quenched with 3 ml of water and 7 ml of ethanol. The organoborane was oxidized with 5 ml of 6 M NaOH and 7 ml of 30% H2O2. The reaction mixture was saturated with anhydrous potassium carbonate, and the organic layer was separated. The aqueous phase was neutralized with 0.1 N HCl and extracted with 20 ml of chloroform twice. The combined organic layers were dried over anhydrous MgSO4 and the solvent removed by rotary evaporation. Acetone was added to effect crystallization to produce a yield of 33%. The product has been identified by co-migration with authentic samples using silica based TLC and capillary GC. Melting point is 174°-175° C. Elemental analysis: Calc. C=79.19, H=10.76. Obs. C=78.86, H=10.70, NMR: 200 MHz ppm delta; 0.59 (s)(CH3), 0.77 (s)(CH3). 0.9-2.0 (m) (CH2), 2.1 (s)(CH3--C=O), 2.5 (t) (17-H), 4.02 (t) (3-H equatorial). The preparation method is a modification of the method shown in Gyermek et al., "Steroids CCCX. Structure-Activity Relationship of Some Steroidal Hypnotic Agents," J. Med. Chem., 11:117-125 (1968).

Provenance & Evidence