Sodium Hydroxide → 5-Hydroxybenzo[b]thiophene-3-carboxylic acid

Temperatur

50 °C

The methoxybenzo[b]thiophene carboxylic acid from Step 5 was slurried in toluene (35 L) and then warmed to 50° C. To an addition funnel containing toluene (9 L) was added boron tribromide (4.3 kg) and then the solution added over 1 hr to the slurry of 5-methoxy-3-benzo[b]thiophenecarboxylic acid. The mixture was aged for 8 hr. The reaction mixture was cooled to room temperature and 15%NaOH was slowly added (16 kg). To the three phase mixture was added 2 kg Solka Flok (filter aid) and then filtered to remove boric acid. The layers were then cut. To the aqueous layer was added 27 L THF and 4.5 kg NaCl, and then acidified to pH=1-3 with concentrated HCl (2.7 L). The layers were cut and the bottom layer extracted again with 15 L THF. The combined THF layers were then concentrated to a minimum stirred volume and solvent switched into toluene (kf<1000 ug/ml). The slurry was then cooled to 2-5° C., aged one hour and filtered, washing with cold toluene (10 L). The cake was dried on the filter pot with a nitrogen sweep under vacuum.

1. temperatureThe reaction mixture was cooled to room temperature
2. additionTo the three phase mixture was added
3. filtration2 kg Solka Flok (filter aid)
4. filtrationfiltered
5. customto remove boric acid
6. additionTo the aqueous layer was added 27 L THF and 4.5 kg NaCl
7. extractionthe bottom layer extracted again with 15 L THF
8. concentrationThe combined THF layers were then concentrated to a minimum
9. temperatureThe slurry was then cooled to 2-5° C., aged one hour
10. filtrationfiltered
11. washwashing with cold toluene (10 L)
12. customThe cake was dried on the filter pot with a nitrogen sweep under vacuum

ORD-Eintrag

ord-dc8ba9248a3b472b8de41597ebb9f46f

Quelldatensatz

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06693203B2