Hydrochloric Acid → 4-Pyrimidinemethanol, 2-amino-

Aqueous HCl (2M, 207 mL, 828 mmol) was added to 4-(dimethoxymethyl)pyrimidin-2-amine (30) (WO 2007096764) (14.0 g, 83 mmol). The mixture was placed in a preheated oil bath at 48° C. for 16 hr. The mixture was cooled to RT and neutralized with solid Na2CO3 which produced a precipitate at pH 7. EtOAc (300 mL) was added, and the solid removed by filtration. After separation of the organic layer, the aqueous layer was extracted with 1% MeOH in THF (4×300 mL). The organics were combined, dried, filtered and evaporated to give crude aldehyde (ca. 4.0 g). This material was suspended in MeOH (100 mL), THF (100 mL) and water (100 mL) and treated with NaBH4 (1.565 g, 41.4 mmol). After stirring for 1 hr NaOH (1M, 20 mL) was added and the mixture was allowed to stand at RT for 48 hr. The solvents were evaporated to give a yellow solid which was partitioned between water (50 mL) and EtOAc (100 mL). The solid formed at the interface was removed by filtration and the aqueous layer was extracted with THF (3×300 mL), dried, filtered and evaporated to give a yellow solid. The material was suspended in THF (100 mL) and MeOH (50 mL) and absorbed onto silica gel (20 g) and subjected to column chromatography (80 g) eluting with 15% MeOH in DCM to give (2-aminopyrimidin-4-yl)MeOH (31) as an off-white solid (720 mg, 7%): m/z 126 (M+H)+ (ES+).

1. customproduced a precipitate at pH 7
2. customthe solid removed by filtration
3. customAfter separation of the organic layer
4. extractionthe aqueous layer was extracted with 1% MeOH in THF (4×300 mL)
5. customdried
6. filtrationfiltered
7. customevaporated
8. customto give crude aldehyde (ca. 4.0 g)
9. additionwas added
10. waitto stand at RT for 48 hr
11. customThe solvents were evaporated
12. customto give a yellow solid which
13. customwas partitioned between water (50 mL) and EtOAc (100 mL)
14. customThe solid formed at the interface
15. customwas removed by filtration
16. extractionthe aqueous layer was extracted with THF (3×300 mL)
17. customdried
18. filtrationfiltered
19. customevaporated
20. customto give a yellow solid
21. customMeOH (50 mL) and absorbed onto silica gel (20 g)
22. washeluting with 15% MeOH in DCM

ORD record

ord-3f8eb7b71d6c4dbf8d853c557bb41d4a

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975285B2