Thymine → 2-(5-Methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)acetic acid

Temperature

0 °C

This procedure is different from the literature synthesis, but is easier, gives higher yields, and leaves no unreacted thymine in the product. To a suspension of thymine (3, 40.0 g; 0.317 mol) and potassium carbonate (87.7 g; 0.634 mmol) in DMF (900 ml) was added methyl bromoacetate (30.00 ml; 0.317 mmol). The mixture was stirred vigorously overnight under nitrogen. The mixure was filtered and evaporated to dryness, in vacuo. The solid residue was treated with water (300 ml) and 4 N hydrochloric acid (12 ml), stirred for 15 min at 0° C., filtered, and washed with water (2×75 ml). The precipitate was treated with water (120 ml) and 2N sodium hydroxide (60 ml), and was boiled for 10 minutes. The mixture was cooled to 0° C., filtered, and the pure title compound was precipitated by the addition of 4 N hydrochloric acid (70 ml). Yield after drying, in vacuo over sicapent: 37.1 g (64%). 1H-NMR: (90 MHz; DMSO-d6): 11.33 ppm (s, 1H, NH); 7.49(d, J=0.92 Hz, 1H, ArH); 4.38 (s, 2H, CH2); 1.76 (d, J=0.92 Hz, T-CH3)

1. filtrationThe mixure was filtered
2. customevaporated to dryness, in vacuo
3. additionThe solid residue was treated with water (300 ml) and 4 N hydrochloric acid (12 ml)
4. stirringstirred for 15 min at 0° C.
5. filtrationfiltered
6. washwashed with water (2×75 ml)
7. additionThe precipitate was treated with water (120 ml) and 2N sodium hydroxide (60 ml)
8. waitwas boiled for 10 minutes
9. filtrationfiltered
10. customthe pure title compound was precipitated by the addition of 4 N hydrochloric acid (70 ml)
11. customYield
12. customafter drying, in vacuo over sicapent: 37.1 g (64%)

ORD record

ord-f2fc8a70a8a24a3ea6c3fb54e41e4cea

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07378485B2