| 36% |
With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; |
3.3.2. Synthesis of ((1S,4R)-((R)-2-(2-bromophenyl)-1,1,1-trifluoropropan-2-yl) 4,7,7-trimethyl-3-oxo-2-oxabicyclo (2.2.1)heptane-1-carboxylate), (R)-c, and ((1S,4R)-((S)-2-(2-bromophenyl)-1,1,1-trifluoropropan-2-yl) 4,7,7-trimethyl-3-oxo-2-oxabicyclo (2.2.1)heptane-1-carboxylate), (R)-c
The compound (1S)-Camphanic chloride (10.02 g, 46.27 mmol) was added to a solutionof 2-(2-bromophenyl)-1,1,1-trifluoropeopan-2-ol, racemic-b, (3.76 g, 14.00 mmol), triethylamine(6.45 mL, 46.27 mmol), and 4-(dimethylamino)pyridine (1.71 g, 14 mmol) in anhydrousdichloromethane (250 mL) at 0 C under nitrogen. After stirring the reaction mixture at roomtemperature for 16 h, the mixture was washed with water, saturated sodium bicarbonate, and thenbrine (50 mL of each). The organic layer was then dried with magnesium sulfate, filtered,and concentrated. The crude residue was purified with column chromatography (petroleumether/dichloromethane, 10:1). The (R)-c, ((1S,4R)-((R)-2-(2-bromophenyl)-1,1,1-trifluoropropan-2-yl)4,7,7-trimethyl-3-oxo-2-oxabicyclo(2.2.1)heptane-1-carboxylate), eluted faster than the (S)-c((1S,4R)-((S)-2-(2-bromophenyl)-1,1,1-trifluoropropan-2-yl) 4,7,7-trimethyl-3-oxo-2-oxabicyclo(2.2.1)heptane-1-carboxylate). (R)-c was (2.17 g, 4.99 mmol, 36% yield). The following procedures wereconducted: 1H NMR (400 MHz, CDCl3, ): 1.05 (s, 6H), 1.14 (s, 3H), 1.68-1.74 (m, 1H), 1.88-1.96(m, 1H), 2.14-2.20 (m, 1H), 2.22 (s, 3H), 2.41-2.47 (m, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.37 (t, J = 7.2 Hz,1H), 7.47 (d, J = 8Hz, 1H), 7.65 (d, J = 7.6Hz, 1H); 13C NMR (100 MHz, CDCl3, ): 9.68, 16.53, 16.77,21.62, 28.81, 30.99, 54.66, 54.97, 83.35 (d, J = 30 Hz), 90.55, 120.73, 123.92 (q, J = 283 Hz), 127.47, 129.73,130.48, 132.87, 136.28, 164.99, 178.14; 19F NMR (376 MHz, CDCl3, ): 77.07 (s); MS (ESI): calc. forC19H20BrF3O4Na (M + Na+): 471.0389, found 471.0380; (S)-c was (1.62 g, 3.72 mmol, 27% yield); 1HNMR (400 MHz, CDCl3, ): 1.01 (s, 3H), 1.13 (s, 6H), 1.73-1.77 (m, 1H), 1.93-1.97 (m, 1H), 2.18-2.25(m, 1H), 2.20 (s, 3H), 2.57-2.61 (m, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.45 (d, J = 8Hz,1H), 7.65 (d, J = 8 Hz, 1H); 13C NMR (CDCl3, ): 9.64, 16.72, 16.86, 21.85, 29.02, 31.07, 54.40, 54.81, 83.29(q, J = 30 Hz), 90.73, 120.63, 124.10 (q, J = 283 Hz), 127.53, 129.59, 130.53, 132.83, 136.29, 164.08, 177.73;19F NMR (376 MHz, CDCl3, ): 76.71 (s); MS (ESI): calc. for C19H20BrF3O4Na (M + Na+): 471.0389,found 471.0382. Crystals of the (S)-c were formed by slow evaporation of the product from diethylether solution. Crystals were good enough for X-ray crystal crystallography. |
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