反应详情

(4-Methoxy-phenyl)-phenylamino-acetic acid hydrochloride (I92) (300 mg, 1.02 mmol), DCC (253 mg, 1.23 mmol), and HOBT (188 mg, 1.23 mmol) are dissolved in THF (10 mL). DIPEA (0.36 mL, 2.04 mmol) and (R)-quinuclidin-3-ol (130 mg, 1.02 mmol) are added. The mixture is stirred ad RT for 16 hours. Then DCC (25.3 mg, 0.12 mmol), HOBT (18.8 mg, 0.12 mmol), DIPEA (36 uL, 0.204 mmol) and (R)-quinuclidin-3-ol (13.0 mg, 0.10 mmol) are added again and reaction is stirred for additional 32 hours. THF is evaporated and the residue is dissolved in EtOAc and washed with sat. NaHCO3, H2O and brine. The organic layer is dried (Na2SO4), filtered and evaporated. The crude residue is purified by flash chromatography (DCM/MeOH=97/3 to 92/8) to obtain the title compound as a yellow solid (90 mg, 24% yield, mixture of diastereoisomers).

1. customreaction
2. stirringis stirred for additional 32 hours
3. customTHF is evaporated
4. dissolutionthe residue is dissolved in EtOAc
5. washwashed with sat. NaHCO3, H2O and brine
6. dry with materialThe organic layer is dried (Na2SO4)
7. filtrationfiltered
8. customevaporated
9. customThe crude residue is purified by flash chromatography (DCM/MeOH=97/3 to 92/8)