Dimethyl Sulfate → Methyl 2-((5-pyrimidyl)methyl)-3-methoxyacrylate

Participants

Reaction Steps

A mixture of methyl 3-(5-pyrimidyl)propionate (13.1 g) and methyl formate (7.1 ml) dissolved in dry dimethoxyethane (20 ml) was added portionwise to a suspension of sodium hydride (60%, 4.0 g) in DME (10 ml) under argon. Reaction initiated rapidly and was stirred for a further 2 h, diluted with dry diethyl ether (50 ml) and filtered. The solid so separated was washed with further diethyl ether (50 ml) and was dried in vacuo to give a solid that was dissolved in dry dimethyl formamide (50 ml) and potassium carbonate (11.3 g) added under argon. A solution of dimethyl sulfate (7.0 ml) was, then added over 1 hour. The mixture was stirred for 18 h and the solvent removed in vacuo. The residue was partitioned between ethyl acetate (200 ml) and water (100 ml). The aqueous layer was re-extracted with ethyl acetate (2×100 ml) and the combined ethyl acetate layers washed with brine (50 ml) and dried over sodium sulfate. The solvent was removed in vacuo to give methyl 2((5-pyrimidyl)methyl)-3-methoxyacrylate (9.1 g).

Provenance & Evidence