4-Toluenesulfonyl chloride → (S)-N-(5-bromo-2-(1-hydroxypropan-2-ylamino)phenyl)-4-methylbenzenesulfonamide

Temperature

0 °C

A 1-L, round bottomed flask fitted with a nitrogen inlet, magnetic stir bar, and thermocouple was charged with (S)-2-(2-amino-4-bromophenylamino)propane-1-ol (47.55 g, 194 mmol), and pyridine (475 mL). The mixture was cooled to 0° C. and p-toluene sulfonyl chloride (37.0 g, 194 mmol) was added in portions of 12.6 and 24.4 g. The internal temperature rose from 1.5 to 15.6° C. following each addition. The reaction mixture stirred at 0° C. for 1.5 h and was then warmed to room temperature. The pyridine was removed under reduced pressure, and the residue was diluted with ethyl acetate (300 mL) and washed with water (100 mL). The combined organic phases were washed with half saturated brine (100 mL) and concentrated under reduced pressure. The residue was dissolved in toluene (250 mL), and the solution concentrated under reduced pressure (in order to remove some residual pyridine). The crude product was purified by column chromatography on silica gel (eluting with 1:1 hexanes-ethyl acetate). The product-containing fractions were combined and concentrated under reduced pressure. Toluene (250 mL) was added, and the mixture was concentrated under reduced pressure to removed trace pyridine. The material was dried under vacuum (ca 17 Torr) to afford (S)-N-(5-bromo-2-(1-hydroxypropan-2-ylamino)phenyl)-4-methylbenzenesulfonamide (88 g, 110%) as a viscous yellow oil that contains 11 wt % toluene. MS (ESI, pos. ion) m/z 399 [M+1]+.

1. customrose from 1.5 to 15.6° C.
2. additioneach addition
3. temperaturewas then warmed to room temperature
4. customThe pyridine was removed under reduced pressure
5. additionthe residue was diluted with ethyl acetate (300 mL)
6. washwashed with water (100 mL)
7. washThe combined organic phases were washed with half saturated brine (100 mL)
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in toluene (250 mL)
10. concentrationthe solution concentrated under reduced pressure (in order
11. customto remove some residual pyridine)
12. customThe crude product was purified by column chromatography on silica gel (eluting with 1:1 hexanes-ethyl acetate)
13. concentrationconcentrated under reduced pressure
14. additionToluene (250 mL) was added
15. concentrationthe mixture was concentrated under reduced pressure
16. customto removed trace pyridine
17. customThe material was dried under vacuum (ca 17 Torr)

ORD record

ord-09eb8ce833e24ca7bc38aa4c971fb3c7

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09422281B2