4-(Bromomethyl)benzonitrile → 3-(4-Cyanophenyl)-2-(pyrrolidin-2-yl)-propionic acid methyl ester

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Reaction Steps

(R)-1-(tert-Butyloxycarbonyl)pyrrolidin-2-yl-acetic acid methyl ester (0.5 g, 2.06 mmol) is treated with lithium bis(trimethylsilyl)amide and 4-bromomethylbenzonitrile (1.0 g, 5.14 mmol) as described in EXAMPLE 1B to give 3-(4-cyanophenyl)-2-(pyrrolidin-2-yl)-propionic acid methyl ester as a mixture of stereoisomers. This material is coupled with biphenyl-4-carboxylic acid to give 2-[1-(Biphenyl-4-carbonyl)-pyrrolidin-2-yl]-3-(4-cyanophenyl)-propionic acid methyl ester (0.5 g, 1.1 mmol). This material is converted to the title compound (0.47 g, 0.83 mmol) by the procedure described in EXAMPLE 1C. 1H NMR (DMSO-d6, 300 MHz) □ 9.35-9.11(m,4H), 7.78-7.32 (m, 13H), 4.52, 4.36(two m, 1H), 3.58, 3.51 (two s, 3H), 3.50-3.25(m,3H), 3.14-2.95(m, 1H), 2.95-2.80(m, 1H), 2.20-1.55(m, 4H). MS m/z: [M+H]+=456

Provenance & Evidence