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0 °C

4-n-butoxy-3,5-dimethoxybenzoic acid represented by Formula 90 (2 g, 7.87 mmol) was slowly added to a solution of (R)-3-aminoquinuclidine chloride represented by Formula 91 (1.57 g, 7.87 mmol, purchased from Sigma-Aldrich Co.) and diisopropylethylamine (4.11 mL, 23.60 mmol) in DMF (5 mL) at room temperature. The reaction mixture was cooled to 0° C. and, after adding 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate methanaminium (HATU, 2.84 g, 7.47 mmol) thereto, the mixture was agitated at room temperature for 18 hours. After removing the reaction solvent under reduced pressure, chloroform/methanol (9:1) was added to the remaining concentrate to prepare a solution and the solution was washed with a potassium carbonate solution, followed by separation to form an organic layer. After drying the organic layer with magnesium sulfate (MgSO4), the solvent was removed again under reduced pressure. The obtained vacuum-concentrated mixture was subjected to separation and purification through column chromatography (chloroform/methanol/ammonia solution, 10:1:0.01) using silica gel (SiO2), resulting in a benzamide compound represented by Formula 3 (VVZ-002; 2.63 g, 92% yield).

1. customAfter removing the reaction solvent under reduced pressure, chloroform/methanol (9:1)
2. additionwas added to the
3. concentrationremaining concentrate
4. customto prepare a solution
5. washthe solution was washed with a potassium carbonate solution
6. customfollowed by separation
7. customto form an organic layer
8. dry with materialAfter drying the organic layer with magnesium sulfate (MgSO4)
9. customthe solvent was removed again under reduced pressure
10. concentrationThe obtained vacuum-concentrated mixture
11. customwas subjected to separation and purification through column chromatography (chloroform/methanol/ammonia solution, 10:1:0.01)