反应详情

A stirred solution of trans-4-(2-ethoxy-2-oxoethyl)-cyclohexanecarboxylic acid (1 g; 4.67 mmol) in anhydrous THF (25 mL) at 0° C. was treated dropwise with oxalyl chloride (1.02 mL; 11.68 mmol) followed by catalytic DMF (50 μL). The reaction was stirred at room temperature for 2 h, concentrated in vacuo, and the residue was redissolved in THF (25 mL). The resultant solution was cooled to 0° C. and treated with (4S,5R)-3-[2-amino-5-(trifluoromethoxy)benzyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (2.58 g; 5.14 mmol) and triethylamine (0.716 mL; 5.14 mmol). The reaction was stirred at room temperature for 1 h, quenched with water and partitioned between EtOAc (100 mL) and H2O (100 mL). The aqueous layer was extracted with EtOAc (3×100 mL) and the combined extracts were washed with brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography, eluting with EtOAc/hexanes, to afford ethyl [trans-4-({[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl]amino}carbonyl)cyclohexyl]acetate as an off-white solid. LCMS=698.9 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 8.94 (s, 1 H), 8.23 (d, J=8.9 Hz, 1 H), 7.92 (s, 1 H), 7.73 (s, 2H), 7.27-7.24 (m, 1 H), 7.02 (s, 1 H), 5.71 (d, J=8.4 Hz, 1 H), 4.78 (d, J=15.5 Hz, 1 H), 4.19-4.12 (m, 3H), 4.07 (d, J=15.6 Hz, 1 H), 2.43-2.37 (m, 1 H), 2.21 (d, J=6.9 Hz, 2 H), 2.07-1.98 (m, 2 H), 1.93-1.83 (m, 3 H), 1.67 (q, J=12.6 Hz, 2 H), 1.26 (t, J=7.2 Hz, 3 H), 1.19-1.11 (m, 2 H), 0.88 (d, J=6.6 Hz, 3 H).

1. concentrationconcentrated in vacuo
2. dissolutionthe residue was redissolved in THF (25 mL)
3. temperatureThe resultant solution was cooled to 0° C.
4. stirringThe reaction was stirred at room temperature for 1 h
5. customquenched with water
6. custompartitioned between EtOAc (100 mL) and H2O (100 mL)
7. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
8. washthe combined extracts were washed with brine (100 mL)
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash silica gel chromatography
13. washeluting with EtOAc/hexanes