Compound 5b

View in PubChem | 1H NMR | 13C NMR | 19F NMR | MDL Molfile | ChemDraw

Compound data: CIF

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To silver fluoride (9.5 mg, 0.0750 mmol, 30.0 mol%), (DHQD)₂PHAL (hydroquinidine 1,4-phthalazinediyldiether) (19.5 mg, 0.0250 mmol, 10.0 mol%) and CsF (76.0 mg, 0.500 mmol, 2.00 equiv) in a 20.0 mL dried Schlenk tube were added DBDMH (71.5 mg, 0.250 mmol, 1.00 equiv), CH₃CN (2.00 mL) and DCM (1.00 mL). Trifluoromethyl 4-fluorobenzenesulfonate (130 µL, 0.750 mmol, 3.00 equiv) was added to the reaction and the resulting mixture was stirred for 30 min at 25 ^oC, then cooled to -20 ^oC. Epiandrosterone acetate (4b) (82.6 mg, 0.250 mmol, 1.00 equiv) in DCM (0.200 mL) was added dropwise and the reaction mixture was stirred at -20 ^oC for further 24 h. The reaction was quenched with saturated aqueous solution of Na₂SO₃ (1.0 mL), then followed by saturated aqueous solution of NH₄Cl (2.0 mL) at -20 ^oC. The aqueous layers were extracted with CH₂Cl₂ (8.0 mL × 3). The combined organic layers were dried over anh. MgSO₄. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica gel, eluting with hexanes/EtOAc 200:1 (v/v), to afford 99.5 mg (5R, 6R)-6-bromo-5-(trifluoromethoxy)-Epiandrosterone acetate (5b) as a white solid (80% yield, r.r.=2.3:1, d.r.>20:1). The major isomer of 5b R_f = 0.4 (hexanes/EtOAc 8:1 (v/v)). NMR Spectroscopy: ¹H NMR (400 MHz, CDCl₃) δ 5.14 – 4.94 (m, 1H), 4.60 (s, 1H), 2.48 (dd, J = 19.7, 9.0 Hz, 2H), 2.33 (d, J = 14.8 Hz, 1H), 2.25 – 2.06 (m, 4H), 2.04 (s, 3H), 2.02 – 1.79 (m, 3H), 1.74 – 1.51 (m, 4H), 1.54 – 1.47 (m, 3H), 1.46 (s, 3H), 1.35 (dd, J = 18.1, 11.2 Hz, 2H), 0.92 (s, 3H). ¹³C NMR (101 MHz, CDCl₃) δ 220.4, 170.3, 121.7 (q, J = 259.3 Hz), 93.5, 69.7, 50.3, 48.4, 47.9, 45.2, 42.0, 35.9, 35.54, 35.46, 32.3, 31.5, 30.0, 26.2, 21.8, 21.4, 20.54, 20.50, 14.1. ¹⁹F NMR (376 MHz, CDCl₃) δ -48.47 (s, 3F). Mass Spectrometry: HRMS-ESI (m/z): Calcd for C₂₂H₃₀BrF₃NaO₄ [M+Na]⁺, 517.1172. Found, 517.1172. [α]_D²⁰= -2.1 (c 0.125, CHCl₃).