反应详情

温度

20 °C

A stirred solution of 4,6-dichloro-5-[(E)-2-(4-methylphenyl)diazenyl]-2-(propylsulfanyl)pyrimidine (Step (3), 1.1 kg) in 2-propanol (16.6 kg) was hydrogenated for 1 h at 40° C./3.2 bar over a platinum on carbon catalyst (0.81 kg, 50% w/w Pt/C). The hydrogen gas pressure was released and the reactor flushed with nitrogen. The reaction mixture was filtered. The collected solid was washed with 2-propanol (1.7 kg) and the combined filtrates were concentrated under reduced pressure. The residual oil was cooled to 20° C. and dissolved in ethyl acetate (5 kg) and water (5.51) was added. The pH of the stirred mixture was adjusted to pH 2 by the addition of 3M aqueous hydrochloric acid (800 ml). The phases were allowed to separate and the aqueous phase was discharged. Water (2.751) was added to the organic phase and the pH was adjusted to 2 by the addition of a small amount of 3M HCl (45 ml). The aqueous phase was separated and the organic phase concentrated under reduced pressure at 30-50° C., to give 4,6-dichloro-2-(propylsulfanyl)-5-pyrimidinamine as a reddish viscous oil containing ethyl acetate that was dissolved in ethanol (8.5 kg). Solvent (6.51 of ethanol/ethyl acetate) was then removed by distillation at reduced pressure. A further portion of ethanol (4.5 kg) leas added to the residue and the distillation repeated to remove 6.5 l of solvent. The ethanol solution of the product was used without further purification in the following step.

1. customthe reactor flushed with nitrogen
2. filtrationThe reaction mixture was filtered
3. washThe collected solid was washed with 2-propanol (1.7 kg)
4. concentrationthe combined filtrates were concentrated under reduced pressure
5. dissolutiondissolved in ethyl acetate (5 kg)
6. additionwater (5.51) was added
7. additionThe pH of the stirred mixture was adjusted to pH 2 by the addition of 3M aqueous hydrochloric acid (800 ml)
8. customto separate
9. additionWater (2.751) was added to the organic phase
10. additionthe pH was adjusted to 2 by the addition of a small amount of 3M HCl (45 ml)
11. customThe aqueous phase was separated
12. concentrationthe organic phase concentrated under reduced pressure at 30-50° C.