反应详情

The compound 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid (120 mg, 0.51 mmol), N-(4-aminomethyl-2-fluorophenyl)methanesulphonamide (110 mg, 0.51 mmol), 4-methylmorpholine (101 mg, 1.02 mmol) and O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (288 mg, 0.65 mmol) (HBTU) were dissolved in DMF (10 ml) and stirred overnight under a nitrogen atmosphere at RT. The solvent was removed under vacuum, the residue taken up in EtOAc and sat. aq. NaHCO3 solution and the phases were separated. The aqueous phase was extracted several times with EtOAc and the combined organic phases were dried over magnesium sulphate and the solvent was removed under vacuum. After purification by column chromatography (silica gel, hexane/EtOAc 2:1), the desired product 8-tert-butyl-1-oxa-2-azaspiro[4.5]dec-2-ene-3-carboxylic acid-(4-tert-butylphenyl)amide was obtained as a trans isomer (30 mg, 13% of the theoretical amount) and cis isomer (100 mg, 45% of the theoretical amount).

1. customThe solvent was removed under vacuum
2. customsat. aq. NaHCO3 solution and the phases were separated
3. extractionThe aqueous phase was extracted several times with EtOAc
4. dry with materialthe combined organic phases were dried over magnesium sulphate
5. customthe solvent was removed under vacuum
6. customAfter purification by column chromatography (silica gel, hexane/EtOAc 2:1)