反应详情

温度

2.5 °C

N-(2-chloroethyl)acetamide (1.21 g) in ethyl acetate (10 mL) was added over 10 min to a stirred suspension of phosphorus pentachloride (2.08 g) in ethyl acetate (2 ml) at 0° C. under nitrogen to give a clear pale straw solution. After 45 min. at 0° C. toluene (12 ml) was added, and ethyl 2-(3-aminophenyl)-3-furoate hydrochloride (1.78 g) was added in one portion into the above solution at 0-5° C. The mixture was stirred at 0-5° C. for 10 min. and then allowed to warm up to 20° C. After 2 h formation of the amidine was essentially complete (HPLC ethyl 2-(3-aminophenyl)-3-furoate hydrochloride <2% (220 nm, a/a). The mixture was cooled to 0-5° C., crushed ice (18 g) was added over 20 min. to destroy phosphorus oxychloride. Ammonium hydroxide (28%, 6.49 mL) was added at a rate that the internal temperature was kept below 25° C. (ca. 15 min). After 1 h at 20° C. additional ethyl acetate (12 ml) added to the above mixture, the organic layer was separated, washed with deionized water (2×12 ml), and concentrated under reduced pressure. The residue was dissolved in acetone (5 ml) and ethyl acetate (5 ml), and treated with oxalic acid (0.72 g) at 40° C. for 30 min. After aging at <20° C. for at least 12 h, the precipitate was collected by filtration, washed with acetone (2×0.5 vol), and dried in vacuo at 45-50° C. to yield 1.9 g (73%) of white solid.

1. customto give a clear pale straw solution
2. temperatureto warm up to 20° C
3. temperatureThe mixture was cooled to 0-5° C.
4. additionwas added over 20 min.
5. customto destroy phosphorus oxychloride
6. additionAmmonium hydroxide (28%, 6.49 mL) was added at a rate that the internal temperature
7. customwas kept below 25° C.
8. custom(ca. 15 min)
9. additionAfter 1 h at 20° C. additional ethyl acetate (12 ml) added to the above mixture
10. customthe organic layer was separated
11. washwashed with deionized water (2×12 ml)
12. concentrationconcentrated under reduced pressure
13. dissolutionThe residue was dissolved in acetone (5 ml)
14. additionethyl acetate (5 ml), and treated with oxalic acid (0.72 g) at 40° C. for 30 min
15. waitAfter aging at <20° C. for at least 12 h
16. filtrationthe precipitate was collected by filtration
17. washwashed with acetone (2×0.5 vol)
18. customdried in vacuo at 45-50° C.