Piperidine → 5-(p-Cyanophenyl)-4-pentynoic acid

Temperature

80 °C

A solution of 4-pentynoic acid (2.15 g, 22 mmol), 4-bromobenzonitrile (3.64 g, 20 mmol), and piperidine (40 mL) was degassed by bubbling nitrogen through the solution for 5 min. prior to the addition of tetrakis(triphenylphosphine) palladium(O) (240 mg, 0.2 mmol). The reaction vial was sealed and warmed to 80° C. for 1.5 hours. After cooling to 23° C., the reaction mixture was diluted with ethyl acetate (200 mL), filtered, and concentrated in vacuo. The residue was diluted with ethyl acetate (300 mL), washed with 5% HCl (2×100 mL), washed with water (1×100 mL), and extracted with 3% sodium carbonate (2×200 mL). The basic aqueous layer was treated with decolorizing carbon, filtered, and acidified to pH=2. The resultant solid was filtered, washed with water, dried, and purified by flash chromatography (gradient ethyl acetate:methylene chloride:acetic acid 1:9:0.005) and fractional recrystallization (methylene chloride-ether) to afford 5-(p-cyanophenyl)-4-pentynoic acid as a white solid: m.p. 149°-152° C.

1. customby bubbling nitrogen through the solution for 5 min.
2. customThe reaction
3. customvial was sealed
4. temperatureAfter cooling to 23° C.
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. additionThe residue was diluted with ethyl acetate (300 mL)
8. washwashed with 5% HCl (2×100 mL)
9. washwashed with water (1×100 mL)
10. extractionextracted with 3% sodium carbonate (2×200 mL)
11. additionThe basic aqueous layer was treated with decolorizing carbon
12. filtrationfiltered
13. filtrationThe resultant solid was filtered
14. washwashed with water
15. customdried
16. custompurified by flash chromatography (gradient ethyl acetate:methylene chloride:acetic acid 1:9:0.005) and fractional recrystallization (methylene chloride-ether)

ORD record

ord-b18dd9c9fcc9477da1017a864dc4e622

Source dataset

uspto-grants-1994_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05344837