Propargyl alcohol → 3-Cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-propionic acid methyl ester

Temperature

70 °C

A solution of 3-cyclopentyl-2-(4-iodo-phenyl)-propionic acid methyl ester (2.15 g, 6.00 mmol) and triethylamine (6 mL, 0.04 mmol) in N,N-dimethylformamide (6 mL) was treated with propargyl alcohol (0.87 mL, 15.0 mmol). The resulting reaction mixture was degassed with argon and then treated with cooper iodide (30 mg, 0.15 mmol) and bis(triphenylphosphine)palladium (II) chloride (45 mg, 0.06 mmol). The reaction was then heated at 70° C. for 24 h. At this time, the reaction was cooled to 25° C. and concentrated in vacuo. The residue was diluted with ethyl acetate (120 mL) and washed with a half-saturated aqueous sodium chloride solution (1×60 mL). The resulting aqueous layer was back extracted with ethyl acetate (1×120 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 60/40 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-[4-(3-hydroxy-prop-1-ynyl)-phenyl]-propionic acid methyl ester (1.57 g, 91%) as an amber oil.

1. customThe resulting reaction mixture
2. customwas degassed with argon
3. temperatureAt this time, the reaction was cooled to 25° C.
4. concentrationconcentrated in vacuo
5. additionThe residue was diluted with ethyl acetate (120 mL)
6. washwashed with a half-saturated aqueous sodium chloride solution (1×60 mL)
7. extractionThe resulting aqueous layer was back extracted with ethyl acetate (1×120 mL)
8. dry with materialThe combined organic extracts were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-9f578754bb3d4ae4a785ef033c0d4012

Source dataset

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06388071B2