Diisopropylamine → 4-Methyl-3-(2-pyridyl)phenyl-pent-4-enoic acid

Temperature

-78 °C

nBuLi (21 ml, 2.5 M in hexanes, 52.16 mmol) was added dropwise to a solution of diisopropyl amine (5.3 ml, 52.5 mmol) in THF (60 ml) at 0 degrees C. The reaction was stirred 20 minutes, then cooled to −78 degrees C. The LDA solution was then added dropwise into a cooled solution of 3-(2-pyridyl)phenyl acetic acid (5.0 g, 23.5 mmol) in THF (20 ml) at −78 degrees C. After addition, the reaction mixture was warmed to 0 degrees C., then cooled again to −78 degrees C. 3-Bromo-2-methylpropene (3.55 ml, 35.2 mmol) was then added rapidly. The reaction mixture was stirred for 1 h. then quenced with water (20 ml). The THF from the reaction mixture was then removed in vacuo, then the pH of the solution was adjusted to 7 by adding con HCl and pH 7 buffer (1 M). The aqueous reaction mixture was then extracted twice with CHCl3. The combined organic extracts were dried with magnesium sulfate, concentrated in vacuo, and chromatographed (silica gel, 3% MeOH-CH2Cl2) to yield a white solid (4.8 g, 77%): MS ES(+) 268.3 (M+H+).

1. additionAfter addition
2. temperaturethe reaction mixture was warmed to 0 degrees C
3. temperature, then cooled again to −78 degrees C
4. stirringThe reaction mixture was stirred for 1 h.
5. customThe THF from the reaction mixture was then removed in vacuo
6. additionby adding con HCl and pH 7 buffer (1 M)
7. extractionThe aqueous reaction mixture was then extracted twice with CHCl3
8. dry with materialThe combined organic extracts were dried with magnesium sulfate
9. concentrationconcentrated in vacuo
10. customchromatographed (silica gel, 3% MeOH-CH2Cl2)

ORD record

ord-7601fbeb095d4eb0abfc689a6ebdb329

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06518267B1