Nitrogen → (2R,5R)-4-[2-(6-Benzyl-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a degassed (N2) solution of LiBr (20 mg, 0.2 mmol) and (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium (II) dichloride (1.0 mg, 0.14 mmol) in anhydrous THF/NMP (1:1, 0.48 mL) was added a solution of (2R,5R)-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-5-hydroxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (65 mg, 0.14 mmol), THF (0.1 mL) and benzylzinc bromide (575 μL, 0.30 mmol). The reaction was stirred for 18 h and diluted with MeOH then loaded onto a SCX column eluting with MeOH and then 2.0 M ammonia-MeOH to release the amine. The solvent was removed in vacuo, to give the title compound (9.0 mg, 12%) as a colourless oil. 1H NMR (Me-d3-OD): 8.03 (1H, s), 7.33-7.03 (6H, m), 6.96 (1H, d), 4.15 (1H, d), 4.10-3.93 (5H, m), 3.76 (1H, dd), 3.67 (1H, d), 3.59-3.49 (2H, m), 2.93-2.83 (2H, m), 2.65 (1H, dd), 1.48 (9H, s), 1.35 (6H, s), 1.23 (3H, d).

Provenance & Evidence