Methyl iodide → 2-(3-(2-Pyridyl)phenyl)-propionic acid

Temperature

0 °C

nBuLi (ml, 2.5 M in hexanes, 52.16 mmol) was added dropwise to a solution of diisopropyl amine (5.2 ml, 37.6 mmol) in THF (20 ml) at −78 degrees C. The reaction was stirred 20 minutes warming to 0 degrees C., then the reaction was cooled to −78 degrees C. The LDA solution was then added dropwise into a cooled solution of 3-(2-pyridyl)phenyl acetic acid (2.0 g, 9.4 mmol) in THF (10 ml) at −78 degrees C. After addition, the reaction mixture was warmed to 0 degrees C., then cooled again to −78 degrees C Methyl iodide (1.2 ml, 18.6 mmol) was then added dropwise. The reaction mixture was stirred for 1 h. then warmed to RT, then quenched 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, 1% AcOH, 3% MeOH—CH2Cl2) to yield a white solid (1.3 g, 61%): MS ES(+) 228.1 (M+H+).

1. temperature, then the reaction was cooled to −78 degrees C
2. additionAfter addition
3. temperaturethe reaction mixture was warmed to 0 degrees C
4. additionwas then added dropwise
5. stirringThe reaction mixture was stirred for 1 h.
6. temperaturethen warmed to RT
7. customquenched with water (20 ml)
8. customThe THF from the reaction mixture was then removed in vacuo
9. additionby adding con HCl and pH 7 buffer (1 M)
10. extractionThe aqueous reaction mixture was then extracted twice with CHCl3
11. dry with materialThe combined organic extracts were dried with magnesium sulfate
12. concentrationconcentrated in vacuo
13. customchromatographed (silica gel, 1% AcOH, 3% MeOH—CH2Cl2)

ORD record

ord-c2c34250826c40998b8bf10e11c73cf5

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06518267B1