Sodium Hydroxide → (rac)-Propionic acid 4-(3-fluoro-4-trifluoromethyl-phenyl)-6,7-dihydro-5H-[2]pyrindin-7-yl ester

A solution of (rac)-4-(3-fluoro-4-(trifluoromethyl)phenyl)-6,7-dihydro-5H-cyclopenta[c]pyridin-7-ol (example 82) (24 mg, 0.081 mmol) and N,N-diisopropylethylamine (0.028 mL, 0.162 mmol) in DMF (0.2 mL) was treated with propionyl chloride (0.021 mL, 0.243 mmol) and the reaction mixture stirred at room temperature. After 15 h, another aliquot of propionyl chloride (0.021 mL, 0.243 mmol) was added, the temperature increased to 50° C. and stirring continued for 2 h. The crude reaction mixture was poured into a 1 M solution of sodium hydroxide (10 mL) and extracted with ethyl acetate (2×15 mL). The combined organic extracts were washed with a sat. solution of sodium chloride (10 mL), dried (Na2SO4), and concentrated under reduced pressure. Purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 3.2 mg (11%) of the title compound as a light brown solid. MS: 354.5 (M+H)+.

1. temperaturethe temperature increased to 50° C.
2. stirringstirring
3. waitcontinued for 2 h
4. customThe crude reaction mixture
5. extractionextracted with ethyl acetate (2×15 mL)
6. washThe combined organic extracts were washed with a sat. solution of sodium chloride (10 mL)
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated under reduced pressure
9. customPurification by preparative HPLC on reversed phase
10. washeluting with a gradient of acetonitrile/water

ORD record

ord-86b095acfd514ba08bf49c02046d5a53

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187429B2