Diisobutylaluminumhydride → N-(4-(hydroxymethyl)-2-iodo-5-(methylthio)phenyl)methanesulfonamide

Temperature

0 °C

To a solution of ethyl 5-iodo-4-(methylsulfonamido)-2-(methylthio)benzoate (crude, from step 2) in dry toluene (200 mL) at 0° C. was added diisobutylaluminium hydride (1.0 M in toluene, 100 mL, 100 mmol) slowly. After addition, the mixture was stirred at 0° C. for 3 h and quenched with methanol/H2O (1/1). The reaction mixture was poured into a vigorously stirred solution of potassium sodium tartrate (1M, 300 mL) and stirred vigorously for 2 h, after which time it settled to two clear phases. The organic layer was separated, and the aqueous layer was extracted with EtOAc (3×200 mL). The combined organic solution was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (0-40% EtOAc/Hexanes) to afford N-(4-(hydroxymethyl)-2-iodo-5-(methylthio)phenyl)methanesulfonamide (11.9 g, 80% yield for two steps). LC-MS m/z 356 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 7.82 (s, 1H), 7.49 (s, 1H), 4.67 (s, 2H), 2.99 (s, 3H), 2.50 (s, 3H).

1. additionAfter addition
2. customquenched with methanol/H2O (1/1)
3. additionThe reaction mixture was poured into a vigorously stirred solution of potassium sodium tartrate (1M, 300 mL)
4. stirringstirred vigorously for 2 h
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with EtOAc (3×200 mL)
7. washThe combined organic solution was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude product was purified by silica gel chromatography (0-40% EtOAc/Hexanes)

ORD record

ord-5054bdd342324f268c9472a98c0bf991

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073931B2