Ethyl Acetate → 3-(4-Bromophenoxy)-6-methoxybenzo[b]thiophene

Temperature

60 °C

To a solution of 3-(4-bromophenoxy)-6-methoxybenzo[b]thiophene 1,1-dioxide (230 g, 626 mmol) in THF (3450 mL) was added DIBAL-H (1.0 M in DCM, 3132 mL, 3132 mmol). The mixture was heated to 60° C. for 18 hours. The mixture was cooled down to 40° C. DIBAL-H (1.0 M in DCM or Toluene, 500 mL, 500 mmol) was added. The mixture was refluxed for 6 hours. DIBAL-H (1.0 M in DCM, 300 mL, 300 mmol) was added. The mixture was refluxed for 8 hours, after which time the reaction was cooled to 0° C. over 2 hours. EtOAc (1226 mL) was added very slowly. Rochelle salt solution (884 g, 626 mmol in 6000 mL water) was slowly added (over 3 hours). The resulting solution was aged at room temperature for 18 hours. The organic layer was separated from the aqueous layer. The aqueous layer was extracted with EtOAc (1000 mL). The combined organic layer was washed with brined, dried with anhydrous Na2SO4 and concentrated in vacuo to afford 3-(4-bromophenoxy)-6-methoxybenzo[b]thiophene (149.8 g, 446.9 mmol, 71% yield) as a white solid which was used without further purification. 1H NMR (400 MHz, CDCl3) δ ppm=3.81 (s, 3 H), 6.46 (s, 1 H), 6.90 (d, J=9.09 Hz, 3 H), 7.16-7.22 (m, 1 H), 7.31-7.40 (m, 2H), 7.46 (d, J=9.09 Hz, 1 H), LC/MS (m/l, MH+): 336.8.

1. temperatureThe mixture was cooled down to 40° C
2. temperatureThe mixture was refluxed for 6 hours
3. temperatureThe mixture was refluxed for 8 hours
4. temperatureafter which time the reaction was cooled to 0° C. over 2 hours
5. customThe organic layer was separated from the aqueous layer
6. extractionThe aqueous layer was extracted with EtOAc (1000 mL)
7. washThe combined organic layer was washed with brined,
8. dry with materialdried with anhydrous Na2SO4
9. concentrationconcentrated in vacuo

ORD record

ord-1a40abc919e548728a0a434fa3490cee

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321746B2