Methanol → 2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acid

A solution of sodium hydroxide (0.62 g, 15.5 mmol) in water (100 mL) was added to a solution of 2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acid, methyl ester (5.62 g, 14.0 mmol) in tetrahydrofuran (100 mL). The solution was stirred overnight at room temperature. Tlc indicated that the reaction was not complete. 1 M NaOH (20 mL) was added and the mixture was heated at reflux for 6 h. Methanol (100 mL) was added and the mixture was stirred overnight at room temperature. Again, tlc indicated that the reaction was not complete so the reaction mixture was heated at reflux for 2 h, 1 M NaOH (100 mL) was added and the solution was heated at reflux for a further 4 h. The reaction mixture was allowed to stand overnight at room temperature, then the solvent was evaporated, and water (100 mL) and 1 M HCl(200 mL) were added. The mixture was stirred for 20 min and then the white solid was filtered off and dried overnight in a vacuum oven (25 mm Hg, 60° C.) to give 2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoic acid (4.84 g, 89%) as a white solid, mp 213-215° C. (dec.).

1. temperaturethe mixture was heated
2. temperatureat reflux for 6 h
3. stirringthe mixture was stirred overnight at room temperature
4. temperaturewas heated
5. temperatureat reflux for 2 h
6. temperaturethe solution was heated
7. temperatureat reflux for a further 4 h
8. waitto stand overnight at room temperature
9. customthe solvent was evaporated
10. additionwater (100 mL) and 1 M HCl(200 mL) were added
11. stirringThe mixture was stirred for 20 min
12. filtrationthe white solid was filtered off
13. customdried overnight in a vacuum oven (25 mm Hg, 60° C.)

ORD record

ord-e88ed58c484141ed8f45f715af697ef0

Source dataset

uspto-grants-2001_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06331640B1