Sodium Hydroxide → N-[(5-chlorothien-2-yl)sulfonyl]-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-dl-norvaline

Temperature

0 °C

The crude 5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-dl-norvaline (0.92 g, 3.56 mmol) and NaOH mixture was dissolved in water (10 ml). The mixture was cooled to 0° C. in an ice bath. 5-Chlorothiophene-2-sulfonyl chloride (0.852 g, 3.9 mmol) was dissolved in THF (10 mL) and added dropwise to the reaction mixture over 10 min. After 60 min, the reaction mixture was allowed to warm gradually to 25° C. and stirred for 16 h. THF was removed in vacuo and the mixture was acidified to pH <2 with 1N HCl. After 15 min, a precipitate began to crash out of the milky white mixture. After 60 min, the mixture was cooled in a refrigerator for 45 min and then filtered. The precipitate was washed with 1N HCl (10 mL) to provide a white solid which gummed out. It was dissolved in EtOAc (100 mL). The aqueous layer washed with EtOAc (3×50 mL) and the organic layers were washed with saturated aqueous NaCl (50 mL). The organic layer was dried over MgSO4, filtered and concentrated to afford N-[(5-chlorothien-2-yl)sulfonyl]-5,5,5-trifluoro-3-(2,2,2-trifluoroethyl)-dl-norvaline as a brown oil (1.3 g, 86.3%). Mass Spectrum (+ESI): 434 (M+H)+.

1. additionadded dropwise to the reaction mixture over 10 min
2. temperatureto warm gradually to 25° C.
3. customTHF was removed in vacuo
4. waitAfter 15 min
5. waitAfter 60 min
6. temperaturethe mixture was cooled in a refrigerator for 45 min
7. filtrationfiltered
8. washThe precipitate was washed with 1N HCl (10 mL)
9. customto provide a white solid which
10. washThe aqueous layer washed with EtOAc (3×50 mL)
11. washthe organic layers were washed with saturated aqueous NaCl (50 mL)
12. dry with materialThe organic layer was dried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-0877960dbed846b888d580377053bb23

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07547725B2