反应详情

A sample of 2-(4-t-butoxy-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile (5.21 g, 19.86 mmol) was dissolved in 50 mL of trifluoroacetic acid, the reaction was stirred under nitrogen for 1 hour at ambient temperature, and the material concentrated to dryness. The residue was dissolved in a mixture of 15.6 mL of DMF and 90 mL of methylene chloride. This solution was cooled in a water bath as 18.8 mL (19.86 mmol) of POCl3 was added, then the reaction was stirred at ambient temperature for 16 hours. The reaction was quenched by pouring it into ice water, and the mixture was extracted with methylene chloride. The aqueous solution was adjusted to pH7 with NaOH and re-extracted with methylene chloride. The extracts were combined and washed with water, dried over MgSO4 and concentrated. The residue was purified by flash chromatography with 1:4 ethyl acetate:hexane to give 3.26 g of 2-(4-chloro-5-fluoro-3-methyl-2-pyridinyl)cyclopropaneacetonitrile as a colorless liquid after removal of the solvents. MS 225, 227 (M+H)+ ; 1H NMR (CDCl3)∂: 0.48 (m, 1H), 0.59 (m, 1H), 0.66 (m, 1H), 0.77 (m, 1H), 1.50 (m, 1H), 2.48 (s, 3H), 3.80 (d, 1H, J=8 Hz), 8.39 (s, 1H). IR (neat) 2240, 1570, 1460 cm-l.

1. concentrationthe material concentrated to dryness
2. dissolutionThe residue was dissolved in a mixture of 15.6 mL of DMF and 90 mL of methylene chloride
3. additionwas added
4. stirringthe reaction was stirred at ambient temperature for 16 hours
5. customThe reaction was quenched
6. additionby pouring it into ice water
7. extractionthe mixture was extracted with methylene chloride
8. extractionre-extracted with methylene chloride
9. washwashed with water
10. dry with materialdried over MgSO4
11. concentrationconcentrated
12. customThe residue was purified by flash chromatography with 1:4 ethyl acetate