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

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).

1. customReaction
2. filtrationfiltered
3. customThe solid so separated
4. washwas washed with further diethyl ether (50 ml)
5. customwas dried in vacuo
6. customto give a solid
7. additionadded over 1 hour
8. stirringThe mixture was stirred for 18 h
9. customthe solvent removed in vacuo
10. customThe residue was partitioned between ethyl acetate (200 ml) and water (100 ml)
11. extractionThe aqueous layer was re-extracted with ethyl acetate (2×100 ml)
12. washthe combined ethyl acetate layers washed with brine (50 ml)
13. dry with materialdried over sodium sulfate
14. customThe solvent was removed in vacuo

ORD record

ord-d103aa5a61754d46b23c6b36d757dc0f

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06417192B1