Ammonium Chloride → HCID 22021867, compound

Temperature

-78 °C

1M Lithium hexamethyldisilazide solution in hexane (13.2 ml) was dissolved in anhydrous tetrahydrofuran (20 ml) under nitrogen atmosphere. The solution was cooled to −78° C. 8-Fluoro-2,3-dihydro-4H-thiochromen-4-one (2.00 g, 11 mmol) was dissolved in tetrahydrofuran (40 ml), the solution was transferred to the dropping funnel and added dropwise over 30 min to the reaction mixture maintaining the temperature below −60° C. An orange clear solution was obtained which was stirred at −78° C. to −65° C. for 2 h. Methyl cyanoformate (0.935 g, 0.87 ml) was dissolved in tetrahydrofuran (2 ml) and added dropwise to the reaction solution. Stirring was continued at low temperature for 1 h, the mixture was then allowed to warm to room temperature. Saturated ammonium chloride solution (20 ml) and water (10 ml) were added, the phases mixed for 5 min and separated. The aqueous phase was washed with ethyl acetate (2×100 ml) and the combined organic phases were dried over magnesium sulphate. The mixture was filtered and the solvent removed under vacuum to give an orange oil. The crude oil was purified by column chromatography; mobile phase: hexanes, gradient to hexanes/ethyl acetate [90:10]. The title compound was isolated as a yellow solid (1.19 g, 4.95 mmol, 45%).

1. additionadded dropwise over 30 min to the reaction mixture
2. temperaturemaintaining the temperature below −60° C
3. customAn orange clear solution was obtained which
4. additionadded dropwise to the reaction solution
5. stirringStirring
6. waitwas continued at low temperature for 1 h
7. temperatureto warm to room temperature
8. additionthe phases mixed for 5 min
9. customseparated
10. washThe aqueous phase was washed with ethyl acetate (2×100 ml)
11. dry with materialthe combined organic phases were dried over magnesium sulphate
12. filtrationThe mixture was filtered
13. customthe solvent removed under vacuum
14. customto give an orange oil
15. customThe crude oil was purified by column chromatography

ORD record

ord-849badeab25e42c8b3d493e2813469e2

Source dataset

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07081456B2