Hydrochloric Acid → 3-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione

Temperature

60 °C

A mixture of 1-methoxymethyl-3-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (40.4 g, 0.16 mol) and isopropanol (200 mL) was heated to 60° C. and added to refluxing concentrated hydrochloric acid (200 mL) at a rate such that the reaction mixture remained at gentle reflux. The mixture was heated 3 hours at reflux and then distilled to remove methanol byproduct. The mixture was heated 4.5 hours at 92° C., cooled to 25° C., poured into water (650 mL), saturated with sodium hydroxide and extracted with ethyl acetate (5×300 mL). The combined extracts were washed with sodium bicarbonate and water and concentrated in vacuo. The residue was recrystallized from toluene/isopropanol (10:1, 55 mL) and the solids were collected, washed with hexanes and dried at 60° C. (15 g 1st crop). The mother liquors were concentrated and the solids were collected, dried (2nd crop) and combined with the first crop to give 3-(3-chloropropyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (19.8 g, 94 mmol), m.p. 145°-147° C.

1. additionadded
2. temperatureThe mixture was heated 3 hours
3. temperatureat reflux
4. distillationdistilled
5. customto remove methanol byproduct
6. temperatureThe mixture was heated 4.5 hours at 92° C.
7. temperaturecooled to 25° C.
8. additionpoured into water (650 mL), saturated with sodium hydroxide
9. extractionextracted with ethyl acetate (5×300 mL)
10. washThe combined extracts were washed with sodium bicarbonate and water
11. concentrationconcentrated in vacuo
12. customThe residue was recrystallized from toluene/isopropanol (10:1, 55 mL)
13. customthe solids were collected
14. washwashed with hexanes
15. customdried at 60° C. (15 g 1st crop)
16. concentrationThe mother liquors were concentrated
17. customthe solids were collected
18. customdried (2nd crop)

ORD record

ord-1db15a71d7894342970ec1ae92112034

Source dataset

uspto-grants-1999_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05859014