2-Chloro-1,3-thiazole-5-carbaldehyde → 1-(2-Chlorothiazol-5-yl)ethanone

温度

-78 °C

2-Chloro-thiazole-5-carbaldehyde (1.00 g., 6.77 mmol) was dissolved in THF (10 mL) and cooled to −78° C. MeMgBr (2.26 mL of a 3.0 M solution in Et2O, 6.78 mmol) was added dropwise. The mixture was stirred at −78° C. for 30 min and then allowed to slowly warm to −20° C. over a further 30 min. The reaction was quenched by the addition of EtOAc (2 mL), allowed to warm to 20° C., and 2 M hydrochloric acid (20 mL) was added. The mixture was poured into water (200 mL) and extracted into DCM (200 mL), dried (Na2SO4) and concentrated. The residue was dissolved in reagent grade acetone (20 mL), cooled in an ice bath, and Jones' reagent (3.0 mL of a 2.67 M solution) was added dropwise. The mixture was stirred for 16 h, allowing to warm to 20° C., and then quenched with IPA (5 mL), poured into saturated aqueous NaHCO3 (200 mL) and extracted with EtOAc (2×100 mL). The EtOAc extracts were dried (Na2SO4) and concentrated to give pure product (800 mg, 73%) as a somewhat volatile white solid.

1. temperatureto slowly warm to −20° C. over a further 30 min
2. customThe reaction was quenched by the addition of EtOAc (2 mL)
3. temperatureto warm to 20° C.
4. addition2 M hydrochloric acid (20 mL) was added
5. additionThe mixture was poured into water (200 mL)
6. extractionextracted into DCM (200 mL)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in reagent grade acetone (20 mL)
10. temperaturecooled in an ice bath
11. additionJones' reagent (3.0 mL of a 2.67 M solution) was added dropwise
12. stirringThe mixture was stirred for 16 h
13. temperatureto warm to 20° C.
14. customquenched with IPA (5 mL)
15. additionpoured into saturated aqueous NaHCO3 (200 mL)
16. extractionextracted with EtOAc (2×100 mL)
17. dry with materialThe EtOAc extracts were dried (Na2SO4)
18. concentrationconcentrated

ORDレコード

ord-3a95939a7482491a869db20a4a4ee316

出典データセット

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07786132B2