反应 #2314316

反应方程式

Triphosgene

4,5-difluoroanthranilic acid

→

6,7-difluoroisatoic anhydride

溶剂

1,4-dioxane

反应条件

后处理

1. 1
   workup.DISTILLATIONSolvent was slowly distilled off at ca. 50° C.
2. 2
   萃取The aqueous layer was extracted with more ethyl acetate (2×50 ml)
3. 3
   洗涤washed with diluted aq. citric acid (pH ca. 4-5), water (30 ml), brine (50 ml)
4. 4
   干燥dried (MgSO4)
5. 5
   其他Solvent was removed in vacuo

实验过程

Triphosgene (0.65 g, 0.22 mmol) was added to 4,5-difluoroanthranilic acid (0.34 g, 0.2 mmol) in dry 1,4-dioxane (30 ml), and the mixture was stirred at rt. for 1 h. Solvent was slowly distilled off at ca. 50° C., and the residue distributed between ethyl acetate (100 ml) and the pH 7 buffer (50 ml). The aqueous layer was extracted with more ethyl acetate (2×50 ml), and combined organic layers washed with diluted aq. citric acid (pH ca. 4-5), water (30 ml), brine (50 ml), and dried (MgSO4). Solvent was removed in vacuo to yield 0.33 g (83%) of 6,7-difluoroisatoic anhydride. The intermediate thus obtained (0.29 g, 1.45 mmol) was stirred with dry potassium carbonate (0.20 g, 1.45 mmol) in dry methanol (30 ml) for 1 h. Most of the solvent was removed in vacuo, and the residue distributed between ethyl acetate (100 ml) and the pH 7 buffer (50 ml). Aqueous layer was adjusted to pH ca. 7 with additional aq. HCl, and extracted with ethyl acetate (2×30 ml). Combined organic layers were washed with water (2×30 ml), brine (50 ml), and dried (MgSO4). Solvent was removed in vacuo to yield 0.24 g (89%) of methyl 4,5-difluoroanthranilate. 1H NMR in CDCl3 (δ,ppm): 3.86 (s, 3 H), 5.72 (br. s, 2 H), 6.43 (m, 1 H), 7.66 (m, 1 H).

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