反应详情

A solution of 35.0 g 5-(tert-butyl-dimethyl-silanyloxy)-3-(tert-butyl-diphenyl-silanyloxy)-2-fluoro-benzaldehyde described in example 3.2 and 8.13 g 4-aminobenzonitrile in 250 ml EtOH was stirred for 1 hr at r.t. Then 13.43 g toluene-4-sulfonylmethyl isocyanide were added. The solution was cooled to 0° C. Subsequently, 25.9 ml of boron trifluoride diethyl etherate were added in a manner such that the temperature did not exceed 5° C. The mixture was stirred for 15 min at 0° C. and for 2 hrs at r.t. and subsequently treated with 25 ml H2O. The solution was stirred at 50° C. over night. The crude product was isolated by extraction with EtOAc and purified by chromatography on silica gel (cyclohexane/EtOAc) to yield 22.38 g (RS)-[3-(tert-butyl-diphenyl-silanyloxy)-2-fluoro-5-hydroxy-phenyl]-(4-cyano-phenylamino)-acetic acid ethyl ester as amorphous, slightly yellow solid.

1. temperatureThe solution was cooled to 0° C
2. customdid not exceed 5° C
3. stirringThe mixture was stirred for 15 min at 0° C. and for 2 hrs at r.t.
4. stirringThe solution was stirred at 50° C. over night
5. custompurified by chromatography on silica gel (cyclohexane/EtOAc)