Dimethyl Sulfoxide → 3-{4-[1-(4'-tert-Butyl-biphenyl-4-ylmethyl)-3-methyl-butyl]-benzoylamino}-propionic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-bromo-4-bromomethyl-benzene (1.80 g, 7.2 mmol) in DMSO (15 ml) is added PBu3 (2.18 g, 10.8 mmol). The resulting mixture is stirred at 60° C. for 23 h. The reaction solution is then cooled down to room temperature, and NaH (432 mg, 10.8 mmol) is added, followed by the addition of 4-(3-methyl-butyryl)-benzoic acid methyl ester (Preparation 2) (1.74 g, 7.92 mmol). The reaction mixture is stirred at room temperature for about 48 h, and then diluted with ethyl acetate. The organic portion is washed with 1N HCl, water, brine, dried over MgSO4, and concentrated. The resulting residue is hydrolyzed in THF using 5N NaOH. The reaction is neutralized with 5N HCl, extracted with diethyl ether. The organic phase is washed with water, dried, filter and concentrated. The resulting residue is taken into dichloromethane (150 ml). To the solution is added triethyl amine (6.41 ml, 46 mmol), followed by the addition of DMAP (5 mg), 3-amino-propionic acid methyl ester hydrochloride (3.21 g, 23 mmol) and EDCI (8.83 g, 46 mmol). The reaction mixture is stirred at room temperature for 2 days. The reaction mixture is loaded on a silica gel column and eluted with a gradient from 0-100% ethyl acetate in hexanes to afford 2.60 g of the titled compound.

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