Reacción #2175497

Ecuación de reacción

2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium

N,N′-Diisopropylethylamine

2,4-Dimethoxybenzoic acid

sodium hydroxide

(S)-(−)-3-Aminoquinuclidine dihydrochloride

→

(S)-2,4-dimethoxy-N-(quinuclidin-3-yl)benzamide

Rendimiento 84.0%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroby removing the ice-water bath for 60 minutes
2. 2
   OtroReaction mixture
3. 3
   Extracciónextracted twice with ethyl acetate
4. 4
   Lavadowas washed with saturated brine solution
5. 5
   Secadodried over sodium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated to crude clear oil
8. 8
   OtroPurification via preparative HPLC

Procedimiento

4.0 ml of DMF, N,N′-Diisopropylethylamine (5.6 ml, 32.14 mmol), and 2,4-Dimethoxybenzoic acid (1.75 g, 9.64 mmol) was added to a flask charged with (S)-(−)-3-Aminoquinuclidine dihydrochloride (1.60 g, 8.03 mmol) and stirred ice-water bath under nitrogen atmosphere. To the mixture was added 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate Methanaminium (3.05 g, 8.03 mmol) then mixture temperature was raised to ambient temperature slowly by removing the ice-water bath for 60 minutes. Reaction mixture was worked up by addition of 1N sodium hydroxide aqueous solution and extracted twice with ethyl acetate, combined organic layer was washed with saturated brine solution, dried over sodium sulfate, filtered, and concentrated to crude clear oil. Purification via preparative HPLC to obtain pure product of (S)-2,4-dimethoxy-N-(quinuclidin-3-yl)benzamide, (1.95 g, 84% yield) 1H NMR (400 MHz, Methanol-D4) δ (ppm): 7.42 (m, 1H), 7.11 (s, 2H), 4.45 (m, 1H), 3.95 (s, 3H), 3.83 (m, 1H), 3.80 (s, 3H), 3.39-3.27 (m, 5H), 2.37 (m, 1H), 2.19 (m, 1H), 2.11 (m, 2H), 2.01 (m, 1H). C16H22N2O3 =290.16 LCMS (M+H): m/z 291

Fuente