Trifluoroacetic acid → (R)-4-((R)-1-(5-hydroxybenzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one

Temperature

65 °C

The crude (R)-4-((R)-1-(5-hydroxybenz o[d]thiazol-7-yloxy)ethyl)-1-((R)-1-(4-hydroxyphenyl)ethyl)pyrrolidin-2-one (˜1 mmol) from the previous step was dissolved in TFA (10 mL, 130 mmol) and the resulting solution was heated to 65° C. After 15 h, additional TFA (5 mL, 65 mmol) was added and the reaction temperature was increased to 70° C. After an additional 2 h, the reaction mixture was concentrated in vacuo and was diluted with EtOAc (50 mL), saturated aqueous NaHCO3 (30 mL) and brine (20 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (50 mL). The combined organic phase was dried over Na2SO4, filtered, and concentrated to afford (R)-4-((R)-1-(5-hydroxybenzo[d]thiazol-7-yloxy)ethyl)pyrrolidin-2-one that was used without further purification. LCMS-ESI+ (m/z): [M+H]+ calcd for C13H15N2O3S: 279.1, found 279.1.

1. temperaturethe reaction temperature was increased to 70° C
2. waitAfter an additional 2 h
3. concentrationthe reaction mixture was concentrated in vacuo
4. additionwas diluted with EtOAc (50 mL), saturated aqueous NaHCO3 (30 mL) and brine (20 mL)
5. customThe phases were separated
6. extractionthe aqueous phase was extracted with EtOAc (50 mL)
7. dry with materialThe combined organic phase was dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-d9a20dd23d054527b53d89ec5fd195d0

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09376441B2