反应详情

A solution of crude cis and trans mixture 20 in a mixture of iPAc and iPA (1.83 wt %, 9.9 kg; 181 g assay as a mixture) was concentrated in vacuo and dissolved in 2-Me-THF (3.6 L). To the solution was added tert-BuOK (66.6 g, 0.594 mol) at room temperature. The suspension was stirred at room temperature for 2 h. The mixture was poured into water (3.5 L) and the organic layer was separated, washed with 15 wt % of aqueous NaCl (3.5 L), dried over Na2SO4, and concentrated to dryness. The residue was suspended with iPAc (275 mL) and heptane (900 mL) at 60° C. The suspension was slowly cooled down to 1° C. The solid was filtered and rinsed with iPAc and heptane (1:3), dried to afford 21 (166 g, 93 wt %; 85%) as crystals. Mp 176-179° C.; 1H NMR (CDCl3, 500 MHz): δ 7.06 (m, 1H), 6.84 (m, 1H), 5.83 (broad s, 1H), 5.58 (broad s, 1H), 4.22 (m, 1H), 3.88-3.79 (m, 2H), 2.77 (m, 1H), 2.25 (m, 1H), 1.46 (s, 9H), 1.08 (d, J=6.4 Hz, 3H); 19F NMR (CDCl3, 376 MHz): δ −117 (d, J=14 Hz), −135 (d, J=20 Hz), −142 (dd, J=20, 14 Hz); 13C NMR (CDCl3, 100 MHz): δ 171.1, 156.6 (ddd, J=245, 6.4, 2.8 Hz), 155.8, 149.3 (ddd, J=248, 14.4, 8.8 Hz), 147.4 (ddd, J=245, 14.2, 3.8 Hz), 118.0 (dd, J=19.3, 14.5 Hz), 115.9 (dd, J=19.2, 10.4 Hz), 111.0 (ddd, J=26.4, 6.0, 4.3 Hz), 79.8, 51.4, 49.5, 34.1, 29.3, 28.3, 18.0; HRMS: m/z calcd for C17H21F3N2O3 381.1396 (M+Na). found 381.1410.

1. concentration181 g assay as a mixture) was concentrated in vacuo
2. dissolutiondissolved in 2-Me-THF (3.6 L)
3. customthe organic layer was separated
4. washwashed with 15 wt % of aqueous NaCl (3.5 L)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated to dryness
7. customwas suspended with iPAc (275 mL) and heptane (900 mL) at 60° C
8. temperatureThe suspension was slowly cooled down to 1° C
9. filtrationThe solid was filtered
10. washrinsed with iPAc and heptane (1:3)
11. customdried