反应详情

2,4,6-trichloropyrimidine-5-carbaldehyde (5 g, 23.6 mmol) in ethanol (75 mL) was cooled to OC. Ethylhydrazine oxalate (3.54 g, 23.6 mmol) was added followed by addition of triethylamine (10 mL). The mixture was stirred at 0 C for 45 minutes and 8-oxa-3-azabicyclo[3.2.1]octane, HCl (3.53 g, 23.6 mmol) was added. The mixture was allowed to warm to room temperature. The mixture was stirred for 16 h and additional triethylamine (10 mL) was added. The mixture was stirred for an additional 2 h, concentrated, dissolved in ethyl acetate and washed with sat. NaHCO3. The aqueous phase was extracted with ethyl acetate and the combined organic layers were washed with 0.1N HCl, dried over MgSO4 and filtered over magnesol. The mixture was concentrated, dissolved in dichloromethane and filtered over magnesol to give 4.564 g (15.5 mmol, 66%) of the crude product. The crude product was purified by trituration from diethyl ether to give 1.86 g (6.3 mmol, 27%) of the title compound as a light yellow solid. The mother liquor was concentrated, applied to a silica gel column and eluted with ethyl acetate in hexanes (20-55%) to give an additional 1.22 g (4.15 mmol) of product. MS: 294.2/296.2 [M+H].

1. stirringThe mixture was stirred for 16 h
2. stirringThe mixture was stirred for an additional 2 h
3. concentrationconcentrated
4. dissolutiondissolved in ethyl acetate
5. washwashed with sat. NaHCO3
6. extractionThe aqueous phase was extracted with ethyl acetate
7. washthe combined organic layers were washed with 0.1N HCl
8. dry with materialdried over MgSO4
9. filtrationfiltered over magnesol
10. concentrationThe mixture was concentrated
11. dissolutiondissolved in dichloromethane
12. filtrationfiltered over magnesol
13. customto give 4.564 g (15.5 mmol, 66%) of the crude product
14. customThe crude product was purified by trituration from diethyl ether