Reaction #10163

Reaction equation

tert-butyl (1R)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate

methyl 2-fluoro-6-iodobenzoate

potassium carbonate

tri-o-tolylphosphine

→

methyl 4′-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-3-fluoro-1,1′-biphenyl-2-carboxylate

Yield 18.9%

Solvents

EtOAc

THF

water

Conditions

Workup

1. 1
   OtherThe reaction vessel was then sealed
2. 2
   Otherplaced into a 90° C.
3. 3
   Otherfor overnight
4. 4
   Temperatureheating
5. 5
   WashThe organics were washed with brine (×4)
6. 6
   Dryingdried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated under reduced pressure
9. 9
   Otherto give an oil
10. 10
    Washeluting with 10–60% EtOAc in hexanes

Procedure

To a stirred solution of tert-butyl (1R)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethylcarbamate (1.0 g, 2.9 mmol) and methyl 2-fluoro-6-iodobenzoate (1.2 g, 4.32 mmol) in 25 mL of a 5:1 THF:water mixture was added potassium carbonate (1.2 g, 8.64 mmol), tri-o-tolylphosphine (350 mg, 1.15 mmol) and lastly palladium acetate (65 mg, 0.29 mmol). The reaction vessel was then sealed and placed into a 90° C. oil bath for overnight stirring and heating. After about 18 hours the reaction mixture was cooled to ambient temperature and then diluted with EtOAc. The organics were washed with brine (×4), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give an oil. This oil was subject to silica gel chromatography eluting with 10–60% EtOAc in hexanes to provide methyl 4′-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-3-fluoro-1,1′-biphenyl-2-carboxylate (205 mg), found to be pure by LC/MS and proton NMR.

Source