反应详情

1-Oxa-2-aza-spiro[4.5]dec-2-ene-3-carbaldehyde (135 mg, 0.807 mmol, as prepared in Example 19, step B) was placed in a 4 mL vial equipped with a magnetic stir bar. 40% Aqueous NaHSO3 (0.8 mL) was added via syringe, and the mixture stirred at rt for 2 h. 5-Methyl-2′-trifluoromethyl-biphenyl-3,4-diamine (246 mg, 0.923 mmol, as prepared in the previous step) was placed in an 8 mL vial equipped with a magnetic stir bar. EtOH (2 mL) was added. The 1-oxa-2-aza-spiro[4.5]dec-2-ene-3-carbaldehyde solution was added to the 5-methyl-2′-trifluoromethyl-biphenyl-3,4-diamine solution. The flask which had contained the 1-oxa-2-aza-spiro[4.5]dec-2-ene-3-carbaldehyde solution was rinsed with EtOH (0.5 mL) and water (0.25 mL), and this was also added to the 5-methyl-2′-trifluoromethyl-biphenyl-3,4-diamine solution. The mixture was heated to 90° C. for 2 h. The mixture was poured into water, and the precipitate was isolated by filtration. The solid was washed with water, dissolved in EtOAc, dried over MgSO4, filtered, and the solvent was removed under reduced pressure. The residue was purified by column chromatography using a 40-g SiO2 pre-packed column eluting with EtOAc/heptane, 0:1 to 3:7, v/v over 30 min, yielding 136 mg (41%) of the title compound. 1H-NMR (400 MHz, d4-MeOH) δ: 7.76 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.5 Hz, 1H), 7.52 (t, J=7.6 Hz, 1H), 7.26-7.49 (m, 2H), 7.03 (br. s., 1H), 2.63 (br. s., 3H), 1.69-1.88 (m, 6H), 1.45-1.63 (m, 4H).

1. customvial equipped with a magnetic stir bar
2. customvial equipped with a magnetic stir bar
3. washwas rinsed with EtOH (0.5 mL) and water (0.25 mL)
4. additionthis was also added to the 5-methyl-2′-trifluoromethyl-biphenyl-3,4-diamine solution
5. temperatureThe mixture was heated to 90° C. for 2 h
6. additionThe mixture was poured into water
7. customthe precipitate was isolated by filtration
8. washThe solid was washed with water
9. dissolutiondissolved in EtOAc
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customthe solvent was removed under reduced pressure
13. customThe residue was purified by column chromatography
14. washeluting with EtOAc/heptane, 0:1 to 3:7, v/v over 30 min