Phenol → HCID 86723994, compound

Participants

Reaction Conditions

Reaction Steps

(2R,5R)-4-[2-(6-chloro-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridin-1-yl)-2-oxo-ethyl]-5-methoxymethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester (100 mg, 0.21 mol), phenol (24 mg, 0.206 mol), K3PO4 (96 mg, 0.43 mmol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (3 mg, 0.01 mmol), Pd(OAc)2 were combined and slurried in toluene (0.714 mL). The reaction was degassed with nitrogen and heated to 100° C. After 18 h the reaction was cooled to RT. MeOH was added and the solution passed through a Phenomenex NH2 column, eluting with MeOH and then 2.0 M ammonia in MeOH to release the amine. The residue was purified by column chromatography on silica gel (gradient elution, 0-100% EtOAc/petrol), to give (75 mg). Further purification by preparative HPLC (basic method), gave the title compound (19 mg, 17%) as a colourless oil. 1H NMR (Me-d3-OD): 7.91 (1H, s), 7.51 (1H, s), 7.42 (2H, t), 7.22 (1H, t), 7.10 (2H, d), 4.22-4.12 (1H, m), 4.05 (2H, q), 3.95 (1H, d), 3.70 (1H, d), 3.60 (1H, dd), 3.52 (1H, d), 3.00 (1H, s), 2.85 (1H, dd), 2.64 (1H, dd), 1.48 (9H, s), 1.43 (6H, s), 1.22 (3H, d).

Provenance & Evidence