Benzoate → 4-(2-Methyl-1,3-thiazol-4-yl)benzoic acid

Temperature

70 °C

A mixture of methyl-4-acetylbenzoate (7.59 g, 43 mmol) and acetic acid (100 mL) was heated to 70° C. The reaction was cooled to 30° C. once the benzoate was dissolved. Bromine (2.2 mL, 43 mmol) was added dropwise over a period of 30 mins. The reaction was stirred at ambient temperature under nitrogen for 19 hrs. Precipitates formed upon cooling with an ice bath. The precipitate was filtered and washed with a cold solution of 1:1 MeOH/H2O. The crude material (5.05 g) was taken to the next reaction without further purification. A solution of 4-bromoacetyl-benzoic acid methyl ester (0.50 g, 1.9 mmol), ethanol (6.5 mL), and thioacetamide (0.29 mg, 3.9 mmol) was refluxed under nitrogen for 5 hrs. After cooling, the reaction was poured onto water (75 mL) and stirred for 10 mins. The precipitate was filtered and washed with water. The product was collected as a pale yellow powder 0.43 g (95%). A solution of 4-(2-methyl-thiazol-4-yl)-benzoic acid methyl ester (400 mg, 1.7 mmol), lithium hydroxide (108 mg, 2.6 mmol), tetrahydrofuran (2 mL), water (2 mL), and methanol (1.5 mL) was stirred at ambient temperature under nitrogen for 16 hrs. The reaction was concentrated, diluted with water (10 mL), acidified with HCl (4 mL, 1M), and extracted with ethyl acetate and methylene chloride. The organic layers were combined, dried on sodium sulfate, and concentrated to give 0.35 g (94%) of 4-(2-methyl-thiazol-4-yl)-benzoic acid, which was used in the preparation of compound 47 of Table 1.

1. dissolutionwas dissolved
2. customPrecipitates
3. customformed
4. temperatureupon cooling with an ice bath
5. filtrationThe precipitate was filtered
6. washwashed with a cold solution of 1:1 MeOH/H2O
7. customThe crude material (5.05 g) was taken to the next reaction without further purification
8. temperatureAfter cooling
9. additionthe reaction was poured onto water (75 mL)
10. stirringstirred for 10 mins
11. filtrationThe precipitate was filtered
12. washwashed with water
13. customThe product was collected as a pale yellow powder 0.43 g (95%)
14. concentrationThe reaction was concentrated
15. additiondiluted with water (10 mL)
16. extractionextracted with ethyl acetate and methylene chloride
17. customdried on sodium sulfate
18. concentrationconcentrated

ORD record

ord-631cb47574d7434cb2eee5cbbb2656ea

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07300934B2