Hydrochloric Acid → 4-Pyrimidinemethanol, 2-amino-

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Reaction Steps

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+).

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