Methanol → 5-(4-Methoxyphenyl)-2-(1,2,3,4-tetrahydroquinolin-7-yl)thiazole-4-carboxylic acid

Temperature

55 °C

To ethyl 2-(1-acetyl-1,2,3,4-tetrahydroquinolin-7-yl)-5-(4-methoxyphenyl)thiazole-4-carboxylate (1K) (0.483 g, 1.11 mmol) and KOH (1.24 g, 22.1 mmol) was added MeOH (10 mL) and water (45 mL). The reaction mixture was allowed to heat to 55° C. and stirred 48 hours. The reaction was monitored by LCMS. To the reaction mixture was added (0.5 g, 8.9 mmol). The reaction mixture was allowed to heat to 55° C. and stirred for 24 hours. The reaction mixture was cooled to rt and concentrated under reduced pressure. To the crude residue was added EtOAc and water. The layers were separated and the aqueous extract was acidified to ˜pH6 with 1N HCl and extracted with EtOAc. The combined organic extracts were washed sequentially with water, brine, dried over MgSO4, filtered, and concentrated under reduced pressure to provide 0.350 g (86%) of the desired product 5-(4-methoxyphenyl)-2-(1,2,3,4-tetrahydroquinolin-7-yl)thiazole-4-carboxylic acid (1L): LC/MS (APCI): m/z 367.0 (M+H).

1. additionTo the reaction mixture was added (0.5 g, 8.9 mmol)
2. temperatureto heat to 55° C.
3. stirringstirred for 24 hours
4. temperatureThe reaction mixture was cooled to rt
5. concentrationconcentrated under reduced pressure
6. additionTo the crude residue was added EtOAc and water
7. customThe layers were separated
8. extractionthe aqueous extract
9. extractionextracted with EtOAc
10. washThe combined organic extracts were washed sequentially with water, brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure

ORD record

ord-39550be039684684ac5bd943ee954a3c

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067928B2