Formaldehyde → 5-(Hydroxymethyl)uracil

A 2-L, three-necked flask equipped with a mechanical stirrer, thermometer, condenser, and nitrogen-inlet bubbler was charged with uracil (185.0 g, 1650 mmol) (Aldrich), paraformaldehyde (61.50 g, 2050 mmol as formaldehyde) (Aldrich), and a solution of potassium hydroxide (86.9%, 59.95 g, 928.5 mmol) (Aldrich) in water (1.445 L). The mixture was stirred at 50–52° C. for 68 hours. TLC analysis indicated complete reaction. After concentration at 60° C./14 mm Hg to a volume of ca. 500 mL, the residue was diluted with acetone (500 mL). The resulting precipitate was collected by filtration, washed with acetone, and dried by suction, then at 50° C./25 mm Hg to give crude 5-(hydroxymethyl)-1,3-dihydropyrimidine-2,4-dione (250 g) as a white solid. The combined mother liquor and washes were concentrated to a volume of ca. 100 mL and a solution of hydroxylamine hydrochloride (27.52 g, 396.0 mmol, Aldrich) in water (100 mL) was added. The resulting precipitate was collected by filtration, washed with acetone, and dried by suction to give second crop of crude 5-(hydroxymethyl)-1,3-dihydropyrimidine-2,4-dione (34 g) as a white solid. The two lots were combined (244 g, 4% overweight) and used directly in the next step.

1. customreaction
2. concentrationAfter concentration at 60° C./14 mm Hg to a volume of ca. 500 mL
3. additionthe residue was diluted with acetone (500 mL)
4. filtrationThe resulting precipitate was collected by filtration
5. washwashed with acetone
6. customdried by suction
7. customat 50° C./25 mm Hg to give crude 5-(hydroxymethyl)-1,3-dihydropyrimidine-2,4-dione (250 g) as a white solid
8. concentrationThe combined mother liquor and washes were concentrated to a volume of ca. 100 mL
9. filtrationThe resulting precipitate was collected by filtration
10. washwashed with acetone
11. customdried by suction

ORD-Eintrag

ord-058e86fe19104b3e93276368ff9bb7d7

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07098332B2