反应详情

A mixture of 5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophene-2-carbaldehyde (Example 1, (ii) step B, 1.5 g), tert-butylcarbamate (1.32 g), trifluoroacetic acid (0.57 ml) and triethylsilane (1.81 ml) in acetonitrile (15 ml) is stirred at room temperature for 20 hours. Additional tert-butylcarbamate (1.32 g), trifluoroacetic acid (0.57 ml) and triethylsilane (1.81 ml) are added and the reaction mixture is stirred at room temperature for a further 24 hours. After diluting with ethyl acetate, the reaction mixture is quenched with a saturated solution of NaHCO3. The organic phase is separated and the aqueous phase is extracted once with ethyl acetate. The combined organic phases are extracted with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl, dried over Na2SO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield {5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-3-methyl-thiophen-2-ylmethyl}-carbamic acid tert-butyl ester (1.28 g) as a light yellow foam. MS (HPLC/MS): 509 (MH+). Retention time: 2.32 min.

1. stirringthe reaction mixture is stirred at room temperature for a further 24 hours
2. customthe reaction mixture is quenched with a saturated solution of NaHCO3
3. customThe organic phase is separated
4. extractionthe aqueous phase is extracted once with ethyl acetate
5. extractionThe combined organic phases are extracted with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl
6. dry with materialdried over Na2SO4
7. concentrationconcentrated in vacuo
8. customThe crude product is purified on a semi-preparative HPLC