Compound 7a

View in PubChem | MDL Molfile | ChemDraw

InChIKey UFAPTLRWCBQZJH-HHHXNRCGSA-N

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

The reaction flask containing powdered molecular sieves 4Å (100 mg) was flame-dried under vacuum. To the flask were added (1e (0.005 mmol, 3.7 mg) and (trifluoromethyl)benzene (1.0 mL) under argon atmosphere and the solution was cooled to the indicated temperature. To the solution were added N’-benzylbenzoylhydrazide 3 (0.10 mmol, 22.6 mg), 2,4-dimethyl-3-pentyl 2-diazoacetate 6 (0.12 mmol, 22.1 mg) and cyclohexanecarboxaldehyde (0.15 mmol, 16.8 mg) After stirring for 20 h at the same temperature, the mixture was treated with sat. NaHCO₃ and extracted with CH₂Cl₂. The combined organic layers were dried over Na₂SO₄and concentrated under vacuum. The residue was then purified by column chromatography on silica gel (eluting with hexane/EtOAc = 5:1) to give 7a as a yellow amorphous solid [84% (42.5 mg)]. Enantiomeric purity was determined by HPLC analysis (Daicel Chiralcel OD-H, hexane/2-propanol = 30:1, flow rate = 0.5 mL/min, retention time; 10.4 min (minor), 11.9 min (major)). ¹H NMR (400 MHz, CDCl₃) δ 8.86 (1H, br), 7.79 (2H, d, J = 7.2 Hz), 7.54 (2H, d, J = 7.2 Hz), 7.50-7.40 (3H, m), 7.35-7.25 (3H, m), 4.72 (1H, t, J = 6.4 Hz), 4.27 (1H, d, J = 13 Hz), 3.85 (1H, d, J = 13 Hz), 3.31 (1H, d, J = 9.2 Hz), 2.39 (1H, m), 2.00-1.90 (3H, m), 1.71-1.57 (4H, m), 1.27-1.05 (3H, m), 0.96-0.85 (14H, m); ¹³C NMR (100 MHz, CDCl₃) δ 168.7, 165.2, 136.6, 133.9, 131.3, 129.2, 128.5, 128.4, 127.6, 127.0, 83.9, 65.6, 59.4, 38.0, 30.7, 30.5, 29.6, 29.5, 26.4, 25.9, 25.7, 19.6, 19.5, 17.21, 17.16 cm^-1; IR (neat) 3279, 2926, 2083, 1663, 1527, 1450,1275, 1115, 1096, 1068 cm-1; HRMS (ESI) exact mass calcd for C₃₀H₄₀N₄O₃: m/z 527.2993 ([M + Na]+), found: m/z 527.2984 ([M + Na]+). [α]²⁶_D = −120.1 (c = 1.0, CHCl₃, 96% ee).