反应详情

A mixture of intermediate (10) (0.019 mol) and Na2CO3 (0.019 mol) in DMF (125 ml) was stirred at room temperature. Methyl 2-bromo-2-phenylacetate (0.01907 mol) was added dropwise. The mixture was stirred for 3 hours. The solvent was evaporated. The residue was taken up in water and DCM. The separated organic layer was dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 100/0; 99.5/0.5) and separated by high performance liquid chromatography over Chiralpak AD (eluent: hexane/ethanol 70/30) in its enantiomers. The desired fractions were collected and the solvent was evaporated, yielding 1-piperidineacetic acid, α-phenyl-4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-, methyl ester, (α1A)-(intermediate 29, mp. 158° C., [α]D20=−28.86° (c=124.95 mg/5 ml in CH3OH)) after crystallisation from 2-propanol and 1-piperidineacetic acid, α-phenyl-4-[4-[[[4′-(trifluoromethyl)[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-, methyl ester, (α1B)-(intermediate 30, mp. 160° C., [α]D20=+27.69° (c=24.38 mg/5 ml in CH3OH)) after crystallisation from 2-propanol.

1. stirringThe mixture was stirred for 3 hours
2. customThe solvent was evaporated
3. customThe separated organic layer was dried
4. filtrationfiltered
5. customthe solvent was evaporated
6. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 100/0; 99.5/0.5)
7. customseparated by high performance liquid chromatography over Chiralpak AD (eluent: hexane/ethanol 70/30) in its enantiomers
8. customThe desired fractions were collected
9. customthe solvent was evaporated