Hydroxylamine → 3-Dimethoxymethyl-1-oxa-2-aza-spiro[4.5]dec-2-ene

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Reaction Steps

To a 40 mL vial equipped with a magnetic stir bar was added DMF (10 mL) and dimethoxy-acetaldehyde (1.50 mL, 10.0 mmol). Aqueous hydroxylamine (0.640 mL, 10.5 mmol) was added via syringe, and the mixture was stirred for 2 h at rt. NCS (1.40 g, 10.5 mmol) was added in small portions as a solid. The mixture was stirred an additional 1 h at rt, diluted with DCM (40 mL), dried over MgSO4, and filtered. The solid was washed with DCM. The filtrate was diluted to a volume of 100 mL and transferred to two 60 mL syringes. Methylene-cyclohexane (2.40 mL, 20.0 mmol), DIPEA (1.92 mL, 11.0 mmol), and DCM (10 mL) were placed in a 200 mL round-bottom flask equipped with a magnetic stir bar. The above-prepared chlorooxime solution was added dropwise with a syringe pump at a rate of 0.0774 mL/min until the addition was complete. The mixture stirred at rt for 3 days, and the solvent was removed under reduced pressure. The residue was dissolved in water (50 mL) and extracted three times with hexanes (25 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The material was used in the next step without purification.

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