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8th August 2013 @ 06:03
Repeat of [blog=3481]Reductive alkylation of glycinamide (PMY 51-2)[/blog] Glycinamide hydrochloride (2.00 g, 18.1 mmol, 1 equiv.) was dissolved in water (2 mL, heated then cooled). Sodium hydroxide (0.77 g, 19.3 mmol, 1.07 equiv) was added. The reaction was stirred for 20 mins but no precipitate formed (as previously described by PMY). Water removed under vacuum to give a white crystalline residue. The residue was stirred in methanol (45 mL) and acetic acid (4.5 mL) to give a hazy partial solution. Benzaldehyde (1.85 mL, 18.1 mmol, 1 equiv.) added and the mixture stirred at room temperature for 20 minutes. Sodium cyanoborohydride (1.25 g, 19.9 mmol, 1.1 equiv.) was added portionwise over 25 minutes and left to stir at room temperature overnight (5.40 pm). After stirring at room temperature for 40 hours the reaction was concentrated under reduced pressure (Reaction mixture dropped in the Buchi Bath - bath basified and disposed) 1M NaOH added to recovered mixture until basic. Extracted with CH2Cl2 (x4). The organic extracts were washed with brine, dried (MgSO4) and concentrated to give an off-white solid (~2 g). Sunday 20:52 Solid dissolved in methanol (40 mL) and AcOH (1 mL). Aqueous formaldehyde (37% wt. 3 mL) added and stirred for 5 minutes. Sodium cyanoborohydride (1.19 g, 19 mmol, 1.05 equiv.) was added portionwise and the reaction mixture left to stir at room temperature. After 36 hours the reaction mixture was concentrated under reduced pressure. 1M NaOH added until basic. Extracted with CH2Cl2 (4 × 30 mL). Extracts washed with brine then dried (MgSO4) and concentrated to a thick very pale yellow oil that solidified at the high vac (1.9 g). Purified by chromatography on silica (2-4% MeOH/DCM). First fraction: AEW 74-1-A = colourless oil [data]7300[/data] Second fraction: AEW 74-1-B = white solid [data]7298[/data] Third fraction: AEW 74-1-C = white solid [data]7302[/data]   First fraction is impurtity, AEW 74-1-B and C look like pure product, ready for hydrogenation and possible submission for testing? NMR Data Intermediate 1 [data]7248[/data][data]7250[/data] Crude Product [data]7284[/data][data]7286[/data] [data]7304[/data][data]7296[/data][data]7294[/data] Hazard and Risk Assessment: See: [blog]2606[/blog] Reaction scaled up from previous by factor of 4 (from 4.5 to 18.1 mmol), but has already been performed on this scale see: [blog=3481]Reductive alkylation of glycinamide (PMY 51-2)[/blog] .
Attached Files
AEW 74-1 proton crude INT.pdf
AEW 74-1
AEW 74-1 crude product 1H NMR.pdf
AEW 74-1 crude
AEW 74-1
AEW 74-1
AEW 74-1-B proton.pdf
AEW 74-1-A proton.pdf
AEW 74-1-C proton.pdf
AEW 74-1