Sodium Carbonate → HCID 86623752, compound

Temperature

50 °C

The THF-Hexane-MTBE solution containing 23 g (93.3 mmol) of 4-(isobutoxysulfonyl)phenylboronic acid was concentrated to a concentration of ca. 7 ml/g. A portion of this solution containing ca. 4.7 g (19 mmol, 0.26 eq) was added to a solution of 15.4 g (75 mmol) of 3-iodopyridine dissolved in 100 ml of degassed tetrahydrofuran. To this solution, tris(dibenzylidene acetone) dipalladium (0) (0.5 g, 0.6 mol %) and degassed aqueous sodium carbonate solution (300 ml, 3 eq) were added. The reaction mixture was heated to ca. 50° C. to initiate the coupling reaction. During the reaction, Pd2(dba)3 (0.5 g per addition) and rich organic concentrate containing 4-(isobutoxysulfonyl)phenylboronic acid (4.7 g, 0.26 eq per addition) were added in several portions until all the 3-iodopyridine was consumed. The reaction mixture was further heated at ca. 55° C. for an additional 4 hours. The reaction mixture was filtered and washed with methyl-tert-butyl ether. The pH of the product-rich aqueous solution was adjusted to ca. 4, treated with trithiacyanuric acid (Ig) and filtered to remove Pd containing by-products. The pH of the product-rich aqueous solution was adjusted to ca. 7 and was saturated with solid NaCl (118 g) to initiate the crystallisation of the product. The salted-out product was dried in vacuo at less than 70° C. For recrystallization, the dried product was dissolved in 350 ml of 190 proof ethanol at ca. 75° C. The solution was filtered and concentrated to ca. 100 ml and cooled to ca. 30° C. to initiate crystallization. About 200 ml of MTBE was added to maximize the yield. The crystal slurry was filtered, washed and dried in vacuo less than 70° C., to give 13.4 g (70% yield) of sodium 4-(3-pyridinyl)benzenesulfonate.

1. concentrationwas concentrated to a concentration of ca. 7 ml/g
2. additionA portion of this solution containing ca. 4.7 g (19 mmol, 0.26 eq)
3. additionwere added
4. customthe coupling reaction
5. concentrationrich organic concentrate
6. customwas consumed
7. temperatureThe reaction mixture was further heated at ca. 55° C. for an additional 4 hours
8. filtrationThe reaction mixture was filtered
9. washwashed with methyl-tert-butyl ether
10. additiontreated with trithiacyanuric acid (Ig)
11. filtrationfiltered
12. customto remove Pd containing by-products
13. customthe crystallisation of the product
14. customThe salted-out product was dried in vacuo at less than 70° C
15. customFor recrystallization
16. dissolutionthe dried product was dissolved in 350 ml of 190 proof ethanol at ca. 75° C
17. filtrationThe solution was filtered
18. concentrationconcentrated to ca. 100 ml
19. temperaturecooled to ca. 30° C.
20. customcrystallization
21. additionAbout 200 ml of MTBE was added
22. filtrationThe crystal slurry was filtered
23. washwashed
24. customdried in vacuo less than 70° C.

ORD record

ord-ce3ab4946e3145d4b1f82505c77c11d9

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08415480B2