Compound 8

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InChIKey WLQZYGFNQLAKCE-MRVPVSSYSA-N

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

N,N’-Diisopropylethyl amine (1.56 mL, 9 mmol) was added to a solution of (R)-(–)-3-hydroxy-4,4,4-trichlorobutyric β-lactone (2.5 g, 13.5 mmol) in CH₂Cl₂ (30 mL) and cooled to 0 ^oC. A solution of hex-5-yn-1-amine 6 (0.87 g, 9 mmol) in CH₂Cl₂ (10 mL) was added dropwise to the above solution at 0 ^oC. The reaction mixture was stirred at 0 ^oC for 1 h, then at ambient temperature (23 ^oC) for an additional 1 h. After the reaction was judged complete by TLC, the solvent was removed by evaporation and the residue was purified by flash column chromatography (EtOAc/hexane: 20-40%) to give amide 8 (2.4 g, 8.4 mmol, 93% yield) as a colorless oil. ¹H NMR (300 MHz, CDCl₃): δ 6.42 (t, J = 5.4 Hz, 1H), 5.48 (br s, 1H), 4.54 (d, J = 9.3 Hz, 1H), 3.26 (ddd, J = 12.9, 6.9, 2.4 Hz, 2H), 2.92 (dd, J = 15.0, 2.4 Hz, 1H), 2.56 (dd, J = 14.7, 9.3 Hz, 1H), 2.19 (dt, J = 6.6, 2.7 Hz, 2H), 1.95 (t, J = 2.4 Hz, 1H), 1.65-1.50 (m, 4H); ¹³C NMR (125 MHz, CDCl₃): δ 170.0, 102.3, 83.9, 79.7, 68.9, 39.2, 37.8, 28.3, 25.5, 18.0; HRMS (ESI+): m/z calcd. for C₁₀H₁₅Cl₃NO₂ [M+H] 286.0168, found 286.0173.