反应 #2200617

反应方程式

sodium hydrogencarbonate

N,N-dimethyl-p-toluidine

phosphorus oxychloride

N,N-dimethyl-p-toluidine

phosphorus oxychloride

9-fluoro-6H-1,3,3a,6-tetraaza-benzo[e]azulen-5-one

→

5-chloro-9-fluoro-4H-1,3,3a,6-tetraaza-benzo[e]azulene

收率 81.3%

溶剂

chloroform

反应条件

后处理

1. 1
   workup.STIRRINGstirring
2. 2
   workup.WAITwas continued for 1 h at 65° C
3. 3
   温度After cooling to ambient temperature the reaction mixture
4. 4
   workup.STIRRINGthe resulting mixture was stirred vigorously for 45 min
5. 5
   其他The layers were separated
6. 6
   萃取the aqueous layers was extracted with chloroform
7. 7
   干燥The combined organic layers were dried over magnesium sulfate
8. 8
   浓缩concentrated
9. 9
   其他Purification
10. 10
    其他by chromatography (SiO2, hexane:ethyl acetate=100:0 to 40:60) and recrystallisation from diisopropyl ether

实验过程

To a suspension of 9-fluoro-6H-1,3,3a,6-tetraaza-benzo[e]azulen-5-one (4.40 g, 20 mmol) in chloroform (250 mL) were added N,N-dimethyl-p-toluidine (12 mL) and phosphorus oxychloride (5.7 mL, 60 mmol), and the resulting mixture was stirred for 20 h at 65° C. Further N,N-dimethyl-p-toluidine (1.2 mL) and phosphorus oxychloride (0.6 mL, 6.3 mmol) were added, and stirring was continued for 1 h at 65° C. After cooling to ambient temperature the reaction mixture was poured onto aqueous sodium hydrogencarbonate (sat., 1 L), and the resulting mixture was stirred vigorously for 45 min. The layers were separated and the aqueous layers was extracted with chloroform. The combined organic layers were dried over magnesium sulfate and concentrated. Purification by chromatography (SiO2, hexane:ethyl acetate=100:0 to 40:60) and recrystallisation from diisopropyl ether afforded 5-chloro-9-fluoro-4H-1,3,3a,6-tetraaza-benzo[e]azulene (3.85 g) as a brown solid which was dissolved in DMF (65 mL) and cooled to −55° C. 1-Chloro-3-isocyanomethyl-benzene (4.00 g, 26.4 mmol), and a solution of potassium tert-butylate (3.15 g, 27.3 mmol) in DMF (15 mL) were added at −50° C. to −55° C. The reaction mixture was stirred for 1 h at −40° C. to −50° C. before allowing to warm to ambient temperature. Acetic acid (1.1 mL) was added, and the mixture was poured onto aqueous sodium hydrogencarbonate (sat., 2 L) and extracted with ethyl acetate. The combined organic layers were washed with aqueous sodium hydrogencarbonate (sat.) and dried over sodium sulfate. Purification by chromatography (SiO2, dichloromethane:ethanol=100:0 to 98.5:1.5) afforded the title compound (1.25 g, 18%) as a white crystalline solid. MS: m/e=352.2 [M+H]+.

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