Potassium Carbonate → Methyl 2-amino-4-fluorobenzoate--hydrogen chloride (1/1)

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Reaction Steps

Triphosgene (3.26 g, 11 mmol) was added to 4-fluoroanthranilic acid (1.55 g, 1.0 mmol) in dry 1,4-dioxane (50 ml), and the mixture was stirred at rt. for 1 h, and then 50° C. for ca. 30 min. Solvent was removed in vacuo, dry methanol (30 ml) added, followed by potassium carbonate (4.42 g, 35 mmol). The mixture was stirred at r.t. for 30 min, and then 2.5 h at 50° C. Inorganic material was filtered off, and the residue distributed between ethyl acetate (150 ml) and the pH 7 buffer (75 ml). Aqueous layer was extracted with ethyl acetate (2×50 ml). Combined organic layers were washed with water diluted aq. sodium bicarbonate (pH ca. 8; 2×50 ml), brine (50 ml), and dried (MgSO4). The organic solution was concentrated in vacuo (to ca. 75 ml), and 1 M hydrogen chloride in ethyl ether (ca. 25 ml) added. The precipitated crystalline product was filtered off, washed with ethyl ether, hexanes, and dried in vacuo. Yield 1.00 g (49%). 1H NMR in 5% CD3OD in CDCl3 (δ, ppm): 3.83 (s, 3 H), 6.55 (m, 1 H), 6.66 (m, 1 H), 7.88 (m, 1 H).

Provenance & Evidence