N,N-Diethylaniline → 4-[(4-Fluorophenyl)ethynyl]pyridine

4-pyridyl-hydroxymethyldiphenylphosphonate (6) (15.3 g, 46 mmol), diethylaniline (4 mL), and phosphorous oxychloride (50 mL) were warmed to 90° C. for 16 h. The reaction was quenched by pouring the reaction mixture over ice (400 g). Potassium carbonate was added until a pH of 8 was obtained for the solution followed by extraction with methylene chloride (3×200 mL). After drying (MgSO4), the reaction was concentrated to afford crude 4-pyridyl-chloromethyldiphenylphosphonate (7) as a solid which was used in the next step without further purification: Mass Spectrum (CI) 360 (MH+). Potassium t-butoxide (3.30 g, 29.2 mmol) was added as a solid to 4-pyridyl-chloromethyldiphenylphosphonate (7) (5.00 g, 13.9 mmol), 4-fluorobenzaldehyde (8) (2.00 g, 15.3 mmol), and THF (70 mL) at 23° C. under argon. After 16 h, the reaction was quenched by adding to water (200 mL) over 3 mm. After adjusting the pH of the solution to 7 with 1 N HCl, the mixture was extracted with ethyl acetate (3×350 mL), and dried (MgSO4). After concentration in vacuo, the residue was purified by flash chromatography (ethyl acetate:methylene chloride 1:1) to afford 1-(4-pyridyl)-2-(4-fluorophenyl)ethyne (1) as a solid: Mass Spectrum (CI) 198 (MH+).

1. customThe reaction was quenched
2. additionby pouring the reaction mixture over ice (400 g)
3. additionPotassium carbonate was added until a pH of 8
4. customwas obtained for the solution
5. extractionfollowed by extraction with methylene chloride (3×200 mL)
6. dry with materialAfter drying (MgSO4)
7. concentrationthe reaction was concentrated
8. customto afford crude 4-pyridyl-chloromethyldiphenylphosphonate (7) as a solid which
9. customwas used in the next step without further purification
10. customthe reaction was quenched
11. additionby adding to water (200 mL) over 3 mm
12. extractionthe mixture was extracted with ethyl acetate (3×350 mL)
13. dry with materialdried (MgSO4)
14. concentrationAfter concentration in vacuo
15. customthe residue was purified by flash chromatography (ethyl acetate:methylene chloride 1:1)

ORD record

ord-79059b7e57c447108fdc7a27b038ff46

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06605634B2