反应详情

To a solution 2-{[3,5-bis(trifluoromethyl)benzoyl]amino}-4-[3-({[(1E)-(4-tert-butylphenyl)methylidene]amino}oxy)propoxy]benzoic acid methyl ester (0.30 g, 0.48 mmol) in ethanol (20 mL) was added 1.0 N, sodium hydroxide solution (4 mL). This mixture was heated to reflux for 20 minutes and then allowed to cool back to room temperature. Water (5 mL) was added to the mixture, it was concentrated to approximately ¼ volume and then partitioned between ethyl acetate and water. The aqueous layer was acidified to approximately pH 3 using 1 N hydrochloric acid. The layers were then separated. The aqueous layer was extracted with two additional portions of ethyl acetate. The organics were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography through silica gel using ethyl acetate/hexanes (10/90 with 1% formic acid gradient to 20/80 with 1% formic acid) and then recrystallized one time from chloroform/hexanes (1/20) to give 2-{[3,5-bis(trifluoromethyl)benzoyl]amino}-4-[3-({[(1E)-(4-tert-butylphenyl)methylidene]amino}oxy)propoxy]benzoic acid (0.13 g, 45%) as a white powder. mp=157.5-158.5° C. 1H NMR (500 MHz, DMSO-d6); δ 13.54 (bs, 1H), 12.54 (s, 1H), 8.51 (s, 2H), 8.45 (s, 1H), 8.32 (d, 1H), 8.21 (s, 1H), 8.00 (d, 1H), 7.50-7.37 (AA′BB′, 4H), 6.83 (dd, 1H), 4.27 (t, 2H), 4.21 (t, 2H), 2.16 (m, 2H), 1.23 (s, 9H). Mass spec (MW 610.55); (ES−) m/z 609.2. Elemental analysis; Calculated for C30H28F6N2O5: C, 59.02; H, 4.62; N, 4.59. Found: C, 58.78; H, 4.52; N, 4.46.

1. temperatureThis mixture was heated
2. temperatureto reflux for 20 minutes
3. concentrationwas concentrated to approximately ¼ volume
4. custompartitioned between ethyl acetate and water
5. customThe layers were then separated
6. extractionThe aqueous layer was extracted with two additional portions of ethyl acetate
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude material was purified by flash chromatography through silica gel
11. customrecrystallized one time from chloroform/hexanes (1/20)