Hydrochloric Acid → (4-Chloro-2-methoxyphenyl)(1,3-thiazol-5-yl)methanol

Temperature

-78 °C

A solution of 4-bromo-2-trimethylsilanyl-thiazole (1.0 g, 4.23 mmol) in THF (8 mL) was cooled to −78° C. n-BuLi (1.68 mL, 2.5M in hexanes, 4.65 mmol) was added dropwise and the resulting solution was stirred at −78° C. for 30 minutes. A solution of 4-chloro-2-methoxy-benzaldehyde in THF (2 mL) was added to the reaction, followed by 30 minutes of stirring at −78° C. The reaction was then allowed to warm slowly to room temperature. 3M HCl (10 mL) was added and the reaction was stirred for 16 hours. The solution was then neutralized with Na2CO3 solution and partitioned between ethyl acetate and water. The combined organic layers were dried (MgSO4), filtered, and concentrated under vacuum. The residue was then purified by flash column chromatography on silica gel with 7:3 hexanes/ethyl acetate to provide 204 mg (19%) of the title compound. MS (ESI) m/e 256 (M+H)+, 1H NMR (DMSO-d6, 300 MHz): □ 8.92 (s, 1H), 7.61 (s, 1H), 7.51 (d, J=7.80 Hz, 1H), 7.03-7.07 (m, 2H), 6.30 (d, J=4.75 Hz, 1H), 6.19 (d, J=4.41 Hz, 1H), 3.81 (s, 3H).

1. additionwas added dropwise
2. waitfollowed by 30 minutes
3. stirringof stirring at −78° C
4. temperatureto warm slowly to room temperature
5. stirringthe reaction was stirred for 16 hours
6. custompartitioned between ethyl acetate and water
7. dry with materialThe combined organic layers were dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customThe residue was then purified by flash column chromatography on silica gel with 7:3 hexanes/ethyl acetate

ORD record

ord-e2d81b0ec02749b6b4d01546197c3f58

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456169B2