Lithium Chloride → Methyl 2-phenylnicotinate

Temperature

90 °C

A mixture of methyl 2-chloronicotinate (3.10 g, 18.1 mmol), phenyltributyltin (6.30 g, 17 mmol), lithium chloride (5.04 g, 120 mmol), and tetrakis(triphenylphosphine)palladium (1.12 g, 1 mmol) in toluene (65 ml) was degassed and then stirred under a nitrogen atmosphere overnight at 90° C. and at reflux for 5 hours. The cooled reaction mixture was filtered, the filtrate evaporated, and the residue partitioned between acetonitrile (50 ml) and hexane (5×20 ml). The combined hexane layers were extracted with hydrochloric acid (lM, 4×10 ml), the extracts washed with ethyl acetate (15 ml), and basified (4M NaOH). The resulting suspension was extracted with dichloromethane (4×10 ml), the combined extracts dried over MgSO4 and evaporated to leave a colourless oil. Meanwhile, the acetonitrile layer from above was evaporated and the residual oil dissolved in diethyl ether (50 ml) and ethyl acetate (25 ml) and the solution extracted with hydrochloric acid (1M, 4×10 ml). Basification of the acid extracts (4M NaOH) and extraction of the resulting suspension with dichloromethane (4×10 ml) followed by drying of the combined extracts with MgSO4 and evaporation gave an oil which was combined with that obtained as described above (2.62 g).

1. customwas degassed
2. temperatureat reflux for 5 hours
3. customThe cooled reaction mixture
4. filtrationwas filtered
5. customthe filtrate evaporated
6. customthe residue partitioned between acetonitrile (50 ml) and hexane (5×20 ml)
7. extractionThe combined hexane layers were extracted with hydrochloric acid (lM, 4×10 ml)
8. washthe extracts washed with ethyl acetate (15 ml), and basified (4M NaOH)
9. extractionThe resulting suspension was extracted with dichloromethane (4×10 ml)
10. dry with materialthe combined extracts dried over MgSO4
11. customevaporated
12. customto leave a colourless oil
13. customMeanwhile, the acetonitrile layer from above was evaporated
14. dissolutionthe residual oil dissolved in diethyl ether (50 ml)
15. extractionethyl acetate (25 ml) and the solution extracted with hydrochloric acid (1M, 4×10 ml)
16. extractionBasification of the acid extracts (4M NaOH) and extraction of the resulting suspension with dichloromethane (4×10 ml)
17. dry with materialby drying of the combined extracts with MgSO4 and evaporation
18. customgave an oil which
19. customthat obtained

ORD record

ord-de00bf42a7ed4071a0efdff63dd101fb

Source dataset

uspto-grants-2002_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06372754B1