Tributylphosphine → 3-{4-[1-(4'-Trifluoromethyl-biphenyl-4-yloxymethyl)-heptyl]-benzoylamino}-propionic acid methyl ester

Participants

Reaction Steps

A solution of 4′-trifluoromethyl-biphenyl-4-ol (213 mg, 0.90 mmol) and 3-[4-(1-hydroxymethyl-heptyl)-benzoylamino]-propionic acid methyl ester (240 mg, 0.72 mmol) in anhydrous toluene (5 mL) is degassed and filled with nitrogen 3 times. Tributylphosphine (270 μL, 1.07 mmol) is added to the reaction mixture under nitrogen at 0° C., followed by addition of 1,1′-(azodicarbonyl)-dipiperidine (271 mg, 1.07 mmol). The reaction mixture is allowed to warm to room temperature and stirred overnight. The mixture is loaded on a silica gel column and purified using hexanes/ethyl acetate. Some racemic ester is hydrolyzed in the next step, and the remaining intermediate ester is sent to chiral chromatography for resolution (see Example 15, Step C). MS (ES): 554.2 [M+H]−.

Provenance & Evidence