Compound 3i

View in PubChem | 1H NMR | 13C NMR | 19F NMR | Racemic HPLC | Scalemic HPLC | 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. Methyl 4-vinylbenzoate (1i) (40.6 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 50:1 (v/v), to afford 64.7 mg (S)-methyl-4-(2-bromo-1-(trifluoromethoxy)ethyl)benzoate (3i) as a white solid (79% yield). R_f = 0.30 (hexanes/EtOAc 20:1 (v/v)). NMR Spectroscopy: ¹H NMR (400 MHz, CDCl₃) δ 8.09 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 5.34 (dd, J = 7.3, 5.2 Hz, 1H), 3.93 (s, 3H), 3.66 (dd, J = 11.2, 7.4 Hz, 1H), 3.56 (dd, J = 11.2, 5.1 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃) δ 166.5, 141.3, 131.3, 130.3, 126.5, 121.5 (q, J = 257.4 Hz), 79.1 (q, J = 2.5 Hz), 52.4, 33.2. ¹⁹F NMR (376 MHz, CDCl₃) δ -58.54 (s, 3F). Mass Spectrometry: HRMS-EI (m/z): Calcd for C₁₁H₁₀BrF₃O₃ [M] 325.9765, Found, 325.9760. 85:15 e.r. HPLC (Phenomenex Lux 5u chiralpak Cellulose-3, i-PrOH/hexane = 4/96, 0.4 mL/min, 220 nm) t₁ = 26.509 min (major), t₂ = 30.962 min (minor). [α]_D²⁰= +22.9 (c 0.25, CHCl₃).