反应详情

Add 3,5-bis(trifluoromethyl)benzylamine (349 mg, 1.15 mmol) followed by titanium isopropoxide (414 mg, 1.46 mmol) to 6-oxo-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester (300 mg, 1.04 mmol) at room temperature under an atmosphere of nitrogen and stir the solution for 14 h. Add methanol (4.3 mL) and sodium borohydride (59 mg, 1.56 mmol) and stir the mixture under nitrogen at room temperature for 45 min. Add 0.1M NaOH and stir for 30 min. Filter through Celite® and wash the residue with ethyl acetate. Separate the organic layer and extract the aqueous with ethyl acetate. Wash the organic layer with brine and dry the organic layers over anhydrous sodium sulfate. Filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford (+/−)isopropyl-6-(3,5-bis-trifluoromethyl-benzylamino)-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylate (443 mg, 83%).

1. stirringstir for 30 min
2. filtrationFilter through Celite®
3. washwash the residue with ethyl acetate
4. customSeparate the organic layer
5. extractionextract the aqueous with ethyl acetate
6. washWash the organic layer with brine
7. dry with materialdry the organic layers over anhydrous sodium sulfate
8. filtrationFilter
9. customremove the solvent under reduced pressure
10. customPurify the residue by flash chromatography
11. washeluting with hexanes/ethyl acetate