Trimethyl borate → HCID 17953808, compound

(Ref: Briner, K; Burkholder, T. P; Conway, R. G; Cunningham, B. E; Finley, D. R; Heinz, L. J; Jesudason, C. D; Kohlman, D. T; Liang, S. X; Xu, Y. C. Preparation and use of serotonergic benzothiophenes. WO 0109126 A1. Chem. Abs. 134:162912). To a solution of 7-bromo-6-fluoro-1-benzothiophene (0.2 g, 0.9 mmol) and trimethylborate (0.2 mL, 1.8 mmol) at −78° C. was added tert-butyllithium dropwise. After 10 mins at −78° C. the reaction was quenched by pouring onto saturated ammonium chloride. This was extracted with ethyl acetate (3×10 mL) and the solvent removed in vacuo from the combined organic extracts. The residue was taken up in ethyl acetate (4 mL) and 10% aqueous hydrochloric acid (4 mL) was added, the mixture was stirred at room temperature for 1 h. The organic layer was separated and the aqueous layer extracted with ethyl acetate (2×10 mL). The combined organic extracts were dried (MgSO4) and the solvent removed in vacuo. The residue was taken up in THF (10 mL), water (2 mL) and cooled to 0° C. then 10% aqueous sodium hydroxide (2 mL) and 28% hydrogen peroxide (1 mL) were added to this and stirred for 0.5 h at 0° C. The mixture was warmed to room temperature and stirred for 2 hours, before a acetic acid (3 mL) was added. The mixture was extracted with ethyl acetate (3×10 mL), dried (MgSO4) and the solvent removed in vacuo, to give a purple solid. This was purified by flash chromatography with a gradient of 0–20% ethyl acetate in iso-hexane to give the title compound (56 mg, 38%); δH (300 MHz, CDCl3) 7.41 (4H, m, ArH).

1. customAfter 10 mins at −78° C. the reaction was quenched
2. additionby pouring onto saturated ammonium chloride
3. extractionThis was extracted with ethyl acetate (3×10 mL)
4. customthe solvent removed in vacuo from the combined organic extracts
5. addition10% aqueous hydrochloric acid (4 mL) was added
6. customThe organic layer was separated
7. extractionthe aqueous layer extracted with ethyl acetate (2×10 mL)
8. dry with materialThe combined organic extracts were dried (MgSO4)
9. customthe solvent removed in vacuo
10. temperaturewater (2 mL) and cooled to 0° C.
11. addition10% aqueous sodium hydroxide (2 mL) and 28% hydrogen peroxide (1 mL) were added to this and
12. stirringstirred for 0.5 h at 0° C
13. temperatureThe mixture was warmed to room temperature
14. stirringstirred for 2 hours, before a acetic acid (3 mL)
15. additionwas added
16. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
17. dry with materialdried (MgSO4)
18. customthe solvent removed in vacuo
19. customto give a purple solid
20. customThis was purified by flash chromatography with a gradient of 0–20% ethyl acetate in iso-hexane

ORD record

ord-67e67d7d711b4209821afa75b4ce7ee0

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07037932B2