Acetic Acid → HCID 135605572, compound

Temperature

95 °C

A 2-L 3-necked round bottomed flask, oven dried and equipped with a mechanical stirrer, an addition funnel, temperature probe, and argon inlet, was charged with compound 71 (34.1 g, 86.2 moles), acetic acid (40.4 mL, 8 eq) and acetic acid-boron trifluoride complex (38 mL). The reaction mixture was heated to 95° C., stirred for 4 hours and then cooled to room temperature. The reaction mixture was diluted with MeOH (200 mL) and quenched with aqueous KOH (10 N, ˜220 mL) to adjust the pH to about 9.5. Potassium bicarbonate (17.9 g) followed by aqueous hydrogen peroxide (30 wt. %, 39 g) was added to the solution. The resulting solution was warmed to 70° C. and stirred for 10 hours. The reaction was cooled to 5–10° C. Sodium bisulfite (16.2 g) was added portion-wise over 30 minutes. The reaction mixture was concentrated in vacuo to remove most of the MeOH. The resulting yellow semi-solid was cooled to −5° C. and concentrated HCl (˜55 mL) added to adjust the pH to 0.15. The resulting solution was extracted with EtOAc (500 mL) and aqueous KOH (10 N, ˜48 mL) added to adjust the pH to ˜11. The solution was stirred for 1 hour and then the pH was adjusted to ˜7 with HCl (4 mL). The reaction mixture was stirred at room temperature for 1 hour and at ˜5° C. for 3 hours. The solid was collected by filtration and dried under high vacuum for 16 hours. The solid was redissolved in water (600 mL) at 90° C. The clear solution was cooled to ˜60–55° C. and seeded with 21. The solution was allowed to cool to room temperature for 5 hours. The resulting white crystalline solid was collected by filtration and dried under vacuum at 50° C. for 16 hours to afford the title compound (12.9 g).

1. customA 2-L 3-necked round bottomed flask, oven dried
2. customequipped with a mechanical stirrer, an addition funnel
3. temperaturecooled to room temperature
4. customquenched with aqueous KOH (10 N, ˜220 mL)
5. additionwas added to the solution
6. temperatureThe resulting solution was warmed to 70° C.
7. stirringstirred for 10 hours
8. temperatureThe reaction was cooled to 5–10° C
9. additionSodium bisulfite (16.2 g) was added portion-wise over 30 minutes
10. concentrationThe reaction mixture was concentrated in vacuo
11. customto remove most of the MeOH
12. temperatureThe resulting yellow semi-solid was cooled to −5° C.
13. additionconcentrated HCl (˜55 mL) added
14. extractionThe resulting solution was extracted with EtOAc (500 mL) and aqueous KOH (10 N, ˜48 mL)
15. additionadded
16. stirringThe solution was stirred for 1 hour
17. stirringThe reaction mixture was stirred at room temperature for 1 hour and at ˜5° C. for 3 hours
18. filtrationThe solid was collected by filtration
19. customdried under high vacuum for 16 hours
20. dissolutionThe solid was redissolved in water (600 mL) at 90° C
21. temperatureThe clear solution was cooled to ˜60–55° C.
22. temperatureto cool to room temperature for 5 hours
23. filtrationThe resulting white crystalline solid was collected by filtration
24. customdried under vacuum at 50° C. for 16 hours

ORD record

ord-af554af24575478d8205fdf7f0b45953

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07034152B2