(3aR,6aR)-1-(4'-Cyano-biphenyl-4-yl)-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid benzyl ester → (3aR,6aR)-4'-(Hexahydro-pyrrolo[3,4-b]pyrrol-1-yl)-biphenyl-4-carbonitrile

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Reaction Steps

The product of Example 1D ((3aR,6aR)-1-(4′-Cyano-biphenyl-4-yl)-hexahydro-pyrrolo[3,4-b]pyrrole-5-carboxylic acid benzyl ester) (750 mg, 1.77 mmole) was refluxed in 10 ml trifluoroacetic acid for 2.5 hours. The solution was concentrated and triturated with dichloromethane. The residue was redissolved in dichloromethane and stirred with sodium bicarbonate powder. The solution was loaded on a silica gel column and purified by chromatography (0.6% ammonium hydroxide and 6% methanol in dichloromethane) to provide the title compound (330 mg, 64%). 1H NMR (CDCl3) δ ppm 7.64 (d, J=2.71 Hz, 4H) 7.51 (d, J=8.81 Hz, 2H) 6.66 (d, J=8.82 Hz, 2H) 4.07-4.17 (m, 1H) 3.50-3.65 (m, 1H) 3.24-3.36 (m, 1H) 2.86-3.10 (m, 5H) 2.15-2.29 (m, 1H) 1.74-1.93 (m, 1H). MS: (M+H)+=290.

Provenance & Evidence