Chlorosulfonic acid → HCID 53248042, compound

4-(pyridin-2-yldisulfanyl)butanoic acid (102 mg, 0.445 mmol) was coevaporated with 1,2-dichloroethane, (2×6 ml) (to remove moisture) and re-dissolved in 6 ml of 1,2-dichloroethane. The resulting solution was then placed in a preheated oil bath (75˜80° C.). To this solution, sulfurochloridic acid (100 μL, ˜3 eq) was added and the resulting mixture was stirred for 5˜8 min. DIPEA (117 μL, 1.5 eq) was then added (to precipitate the product) and the resulting mixture was stirred for 5 min. Another portion of sulfurochloridic acid (40 ul, 1.33 eq) was added and the mixture was stirred for ˜15 min, followed by addition of DIPEA (63 μL, 0.81 eq) and stirred for 5 min. A third portion of sulfurochloridic acid (40 ul, 1.33 eq) was added and the mixture was stirred for 15˜20 min. The resulting mixture was removed from the oil bath and cooled (on ice bath). Aqueous NaOH (0.5 M) or concentrated Na2CO3 was added to raise the pH ˜12 and the reaction mixture was stirred for 10 min. The organic phase was separated, washed with water (2×10 ml), and neutralized with H3PO4 to pH 7. The organic phase was then concentrated to ˜5 ml and acidified with HCl to pH ˜4. The crude product was purified by passing through a C-18 column using eluting with a gradient of 100% water (containing 0.5% HAc) to 75% of water (containing 0.5% HAc)/25% of MeOH. Fractions containing the desired product (eluted out at 5˜10% of MeOH) were pooled, evaporated to afford 4-(pyridin-2-yldisulfanyl)-2-sulfobutanoic acid (67 mg, 0.217 mmol, 48.7% yield). 1H NMR (D2O) 8.41 (dd, 1H, J=1.5, 4.9 Hz), 7.89 (m, 2H), 7.31 (m, 1H), 3.75 (dd, 1H, J=5.1, 9.6), 2.97 (m, 1H), 2.82 (m, 1H), 2.28 (m, 2H); 13C NMR 176.60, 160.28, 150.60, 140.27, 123.39, 122.92, 69.07, 37.56, 29.45; ESI MS m/z—307.8 (M-H).

1. customThe resulting solution was then placed in a preheated oil bath
2. custom(75˜80° C.)
3. customto precipitate the product) and the resulting mixture
4. stirringwas stirred for 5 min
5. stirringthe mixture was stirred for ˜15 min
6. stirringstirred for 5 min
7. stirringthe mixture was stirred for 15˜20 min
8. customThe resulting mixture was removed from the oil bath
9. temperaturecooled (on ice bath)
10. additionAqueous NaOH (0.5 M) or concentrated Na2CO3 was added
11. temperatureto raise the pH ˜12
12. stirringthe reaction mixture was stirred for 10 min
13. customThe organic phase was separated
14. washwashed with water (2×10 ml)
15. concentrationThe organic phase was then concentrated to ˜5 ml
16. customThe crude product was purified
17. washusing eluting with a gradient of 100% water (containing 0.5% HAc) to 75% of water (containing 0.5% HAc)/25% of MeOH
18. additionFractions containing the desired product (
19. washeluted out at 5˜10% of MeOH)
20. customevaporated

ORD record

ord-0fc77bd6363c4bc3ae9f75ca333c37d2

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598362B2