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26th November 2010 @ 00:29
Scale-up of the racemic resolution of [i]rac[/i]-PZQamine under (semi) optimized conditions of former experiments See related experiments: [*] [url=http://www.ourexperiment.org/racres_pzq/1237]Racemic resolution of praziquanamine with (-)-Dibenzoyl-L-tartaric acid (MW49-5 - MW49-11)[/url] [*] [url=http://www.ourexperiment.org/racres_pzq/1206]Racemic resolution of praziquanamine with (+)-Dibenzoyl-D-tartaric acid (MW49)[/url] [*] [url=http://www.ourexperiment.org/racres_pzq/687]Synthesis of (-)-Dibenzoyl-L-tartaric acid (MW10-1-30)[/url] -> [i]S[/i]-(+)-PZQamine [*] [url=http://www.ourexperiment.org/racres_pzq/1110]Diastereomeric salt resolution of praziquanamine with (-)-di-p-anisoyl-L-tartaric acid obtainig [i]S[/i]-(+)-PZQamine (MW47-3)[/url] [data=size:500x180]667[/data] Start time: 12:10 PM 26/11/2010 End time: 1:40 PM 26/11/2010 [b]Procedure:[/b] [url=http://www.thesynapticleap.org/node/296][i]rac[/i]-Praziquanamine[/url] (1.27 g, 6.27 mmol, M.W. 202.1 g/mol) and [url=http://www.ourexperiment.org/racres_pzq/687](-)-dibenzoyl-L-tartaric acid* 2 [i]i[/i]-PrOH[/url] (3.00 g, 6.27 mmol, M.W. 478.5 g/mol) were dissolved in a mixture of [i]i[/i]-PrOH (60 mL) and water (12 mL) by heating the stirred mixture. After 90 min at room temperature the crystals were filtered off: [u]diastereomeric salt:[/u] Yield 1.55 g (2.76 mmol, 44%) m.p. 145.5-147.5°C [α]D20 = -123° (c = 1, DMSO) [u]liberated amine:[/u] [α]D20 = -242° (c = 1, DCM) -> 82% [i]ee[/i] - After further 3 h the formed crystals were filtered off: 267 mg (8%) m.p. 145-147°C - salt [α]D20 = -110° (c = 1, DMSO) - liberated amine: [α]D20 = -220° (c = 1, DCM) -> 74% [i]ee[/i] [u]mother liquor[/u]: diastereomeric salt: 2.76 g liberated amine 501 mg (2.48 mmol, 40%) [α]D20 = +247° (c = 1, DCM) -> 83% [i]ee[/i] 1H NMR: [data=text]689[/data] - M.W. diastereomeric salt = 560.6 g/mol) [u]2. Crystallization [/u] Start time: 2:40 PM 2/12/2010 End time: 3:30 PM 2/12/2010 The salt (1.33 g, 2.37 mmol) was dissolved in a mixture of i-PrOH (20 mL) and water (10 mL) by heating. After 50 min the precipitate was filtered off. [u]diastereomeric salt:[/u] Yield: 1.20 g (90%, overall: 40%) m.p. 147-148.5°C - liberated amine: [α]D20 = -279° (c = 1, DCM) -> 94% [i]ee[/i]!!! (100 mg salt for liberation) [u]3. Crystallization [/u] Start time: 1:20 PM 3/12/2010 End time: 2:30 PM 3/12/2010 The salt (1.08 g, 1.93 mmol) was dissolved in a mixture of i-PrOH (20 mL) and water (10 mL) by heating. After 50 min the precipitate was filtered off. [u]Yield:[/u] 927 mg (86%) m.p. 147-148.5°C - liberated amine (865 mg salt): 271 mg (1.34 mmol, 21%) [α]D20 = -303° (c = 1, DCM) -> 100% [i]ee[/i] !!! [u]Recovering of the resolving agent:[/u] The basic aq. solution (after PZQamine was extracted) was made acidic to pH ~1 by adding 2 N HCl solution and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and evaporated under reduced pressure. Yield 873 g (7.16 mmol, 57%, M.W. 122.1 g/mol) colorless solid benzoic acid -> hydrolysis of the (-)-Dibenzoyl-L-tartaric acid (under basic conditions) 1H NMR: [data=text]691[/data] 13C NMR: [data=text]693[/data] -> too basic conditions / change order of extraction first acidic, then basic remain 2./3. crystallization, liberated amine 71 mg
Attached Files
1H NMR MW49-12 remain 1. crystallization.pdf
1H NMR MW49-12 recovered resolving agent.pdf
13C NMR MW49-12 recovered resolving agent.pdf