Reaction #7903

Reaction equation

(S)-2-[5-bromo-2-oxo-3-(4-trifluoromethylbenzoylamino)-2H-pyridin-1-yl]-3-phenylpropionic acid methyl ester

(S)-2-[5-Bromo-2-oxo-3-(4-trifluoromethylbenzoylamino)-2H-pyridin-1-yl]-3-phenylpropionic acid methyl ester

1-naphthyleneboronic acid

cesium fluoride

→

title compound

Yield 81.0%

(S)-2-[5-Naphthalen-1-yl-2-oxo-3-(4-trifluoromethylbenzoylamino)-2H-pyridin-1-yl]-3-phenylpropionic acid methyl ester

Yield 81.0%

Solvents

tetrahydrofuran

diethyl ether

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureto reflux for 15 h
3. 3
   Washwashed with saturated ammonium chloride solution and brine
4. 4
   OtherThe organic layer was separated
5. 5
   Dryingdried with sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   OtherPurification by medium pressure liquid chromatography on silica gel (1:5 ethyl acetate/hexanes)

Procedure

A mixture of (S)-2-[5-bromo-2-oxo-3-(4-trifluoromethylbenzoylamino)-2H-pyridin-1-yl]-3-phenylpropionic acid methyl ester from Step E (66.8 mg, 0.128 mmol), 1-naphthyleneboronic acid (44.0 mg, 0.256 mmol), cesium fluoride (97 mg, 0.64 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform complex (13.0 mg, 0.013 mmol) and bis(tri-t-butylphosphine)palladium(0) (16.0 mg, 0.031 mmol) in tetrahydrofuran (2.0 mL) was heated to reflux for 15 h. The reaction mixture was cooled to room temperature, diluted with diethyl ether (100 mL), washed with saturated ammonium chloride solution and brine. The organic layer was separated, dried with sodium sulfate, filtered and concentrated. Purification by medium pressure liquid chromatography on silica gel (1:5 ethyl acetate/hexanes) gave 59 mg (81%) of the title compound as a semisolid. MS 571.2 (M+H)+.

Source