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 h. TLC analysis indicated complete reaction. After concentration at 60° C./14 mmHg 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 mmHg 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 mmHg 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 mmHg 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 기록

ord-3a033b9a8a09491ca1a0fe7d07fca5cf

출처 데이터셋

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07084270B2