p-Toluenesulfonic acid → Ethyl acetate hexane

Participants

Reaction Steps

Aldehyde 6 (2 g, 6.4 mmol, 1 equiv) and N-(2-hydroxyethyl)-2,2,2-trifluoroacetamide (7.37 g, 44.8 mmol, 7 equiv) were dissolved in dry THF (30 mL) followed by addition of p-Toluenesulphonic acid (0.21 g, 1.24 mmol, 0.16 equiv) and 5 Å molecular sieves (30 g). The reaction mixture was stirred overnight and quenched with triethylamine the next day. Molecular sieves from the reaction mixture were removed by filtering with a buckner funnel. A 150 mL portion of water was added to the filtrate and the reaction mixture was extracted with 5×150 mL portion of ethyl acetate. The ethyl acetate was evaporated and the yellow oil was loaded onto the silica gel column. The product was purified by eluting the column with 2/1 hexane/ethyl acetate, 1/1 hexane/ethyl acetate, 1/2 hexane/ethyl acetate and finally with ethyl acetate alone to afford light yellow colored solid. The product was recrystallized twice from ethyl acetate/hexane (1.9 g, 48% yield). Mp: 87.5-88.9° C. IR (cm−1): 3306 (b), 2886 (s), 1714 (s), 1564 (s), 1157 (s). 1H NMR (300 MHz, CDCl3): δ3.34 (s, 3 H), 3.36-3.65 (m, 8 H), 3.71-3.84-3.73 (m, 12 H), 3.79 (t, 2 H, J=4.8), 4.09 (t, 2 H, J=5.2), 5.49 (s, 1 H), 7.1 (m, 3 H,), 7.25 (m, 1 H), 9.85 (s, 1 H). 13C NMR (CDCl3) δ 42.60, 56.12, 61.34, 64.44, 69.31, 70.32, 70.75, 71.07, 71.67, 100.57, 114.82, 117.81, 121.57, 123.05, 129.15, 137.62, 156.40 (q, J=35), 164.2 (s). Calcd: [M+H]+ (C24H35O9F6N2) m/z=609.224. Found FAB-HRMS: [M+H]+=609.2246. Anal. Calcd: C, 47.37; H, 5.63; N, 4.60. Found C, 47.68; H, 5.32; N, 4.53.

Provenance & Evidence