Hydrochloric Acid → HCID 54678507, compound

Temperature

-78 °C

To a solution of γ-butyrolactone (15.5 g, 178.0 mmol) in THF (100 mL) at −78° C. was added a 1.0 M THF solution of LiHMDS (356 mL, 356 mmol), and the resulting mixture stirred at −78° C. for 1.5 hours. A solution of 5-chlorosalicylic methyl ester (16.6 g, 98% purity, 89.0 mmol) in THF (95 mL) was added. After stirring for 1 hour at 0° C., the mixture was warmed to room temperature overnight to ensure complete reaction. After cooling to 0° C., conc. HCl (12 N, 150 mL) was slowly added to bring the pH to 1. The reaction solution was stirred until HPLC analysis indicated the absence of the keto-ester intermediate. To the mixture was added 400 mL CH2Cl2 and 300 mL H2O; the organic phase was separated and the aqueous layer was extracted with CH2Cl2 (100 mL). The organic layers were combined and dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure to give a solid. Heptane (165 mL) was added to a solution of the solid in THF (290 mL) to crystallize the product. After cooling to 0-5° C. for about 3 hours, the product was isolated by filtration and washed with heptane. After drying in vacuo, a total of 13.9 g (66% yield) of the title compound as off-white crystals was obtained. m.p. 185-186° C.; MS m/z 240;

1. stirringAfter stirring for 1 hour at 0° C.
2. temperaturethe mixture was warmed to room temperature overnight
3. customreaction
4. temperatureAfter cooling to 0° C.
5. stirringThe reaction solution was stirred until HPLC analysis
6. customthe organic phase was separated
7. extractionthe aqueous layer was extracted with CH2Cl2 (100 mL)
8. dry with materialdried over anhydrous Na2SO4
9. customthe solvent was removed under reduced pressure
10. customto give a solid
11. customto crystallize the product
12. temperatureAfter cooling to 0-5° C. for about 3 hours
13. customthe product was isolated by filtration
14. washwashed with heptane
15. customAfter drying in vacuo

ORD record

ord-3b2c200b365e457aa0fde6805d87e513

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353119B1