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8th August 2013 @ 06:03
Aew: 60-80

Repeat of Reductive alkylation of glycinamide (PMY 51-2)

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 (xg).

Purified by chromatography on silica (2-4% MeOH/DCM).


Hazard and Risk Assessment:

See: Synthesis of amine-linked analogue of TCMDC-123812 via reductive amination using sodium cyanoborohydride (PMY 38-4) 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: Reductive alkylation of glycinamide (PMY 51-2) .