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

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).

1. wait50° C. for ca. 30 min
2. customSolvent was removed in vacuo, dry methanol (30 ml)
3. additionadded
4. stirringThe mixture was stirred at r.t. for 30 min
5. custom2.5 h
6. customat 50° C
7. filtrationInorganic material was filtered off
8. extractionAqueous layer was extracted with ethyl acetate (2×50 ml)
9. washCombined organic layers were washed with water diluted aq. sodium bicarbonate (pH ca. 8; 2×50 ml), brine (50 ml)
10. dry with materialdried (MgSO4)
11. concentrationThe organic solution was concentrated in vacuo (to ca. 75 ml), and 1 M hydrogen chloride in ethyl ether (ca. 25 ml)
12. additionadded
13. filtrationThe precipitated crystalline product was filtered off
14. washwashed with ethyl ether, hexanes
15. customdried in vacuo

ORD record

ord-c6b5a8d27e8f44dbae025543a36ef9cf

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06413724B1