反应详情

温度

0 °C

To a slurry of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidine carboxylic acid (6.20 g, 24.6 mmol) and N,N-dimethylformamide (0.10 mL, 1.3 mmol) in dichloromethane (200 mL) at ~0° C. under nitrogen atmosphere is added oxalyl chloride (3.30 mL, 37.8 mmol) dropwise. The resulting mixture is stirred 1 hour at 0° C., warmed to room temperature, and stirred an additional 2 hours. The solvent is removed under vacuum and tetrahydrofuran (200 mL) added to the residue. This mixture is cooled to ~0° C. and a solution of N,O-dimethyl-hydroxylamine hydrochloride (2.64 g, 27.1 mmol) and 1-methylpiperidine (3.30 mL, 27.2 mmol) in dichloromethane (100 mL) is added dropwise. After warming to room temperature, the mixture is stirred 16 hours, diluted with dichloromethane (200 mL), and washed with aqueous 0.1N HCl, saturated sodium bicarbonate, and brine solutions. The organic layer is concentrated and the residue recrystallized from ethyl acetate and hexane to give 4.26 g (58%) of the title compound, mp 137°-138° C.

1. temperaturewarmed to room temperature
2. stirringstirred an additional 2 hours
3. customThe solvent is removed under vacuum and tetrahydrofuran (200 mL)
4. additionadded to the residue
5. temperatureThis mixture is cooled to ~0° C.
6. temperatureAfter warming to room temperature
7. stirringthe mixture is stirred 16 hours
8. washwashed with aqueous 0.1N HCl, saturated sodium bicarbonate, and brine solutions
9. concentrationThe organic layer is concentrated
10. customthe residue recrystallized from ethyl acetate and hexane