Triethylamine → (rac.)-(1R*,5S*)-6-{[2-Chloro-5-(3-methoxy-propyl)-benzyl]cyclopropyl-carbamoyl}-7-{4-[2-(2,6-dichloro-4-methyl-phenoxy)-ethyl]-phenyl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,9-dicarboxylic acid di-tert-butyl ester

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Reaction Steps

(rac.)-(1R*,5S*)-7-{4-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethyl]-phenyl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester (300 mg, 0.463 mmol) was dissolved in toluene (10 if L). DMF (1.8 μL) and oxalyl chloride (52.7 μl, 0.6 mmol) were added. The mixture was stirred at rt for 1 h. The solvents were thoroughly removed under reduced pressure, and the residue was dissolved in CH2Cl2 (7.5 μL). A sol. of [2-chloro-5-(3-methoxy-propyl)-benzyl]-cyclopropyl-amine (176 mg, 0.693 mmol) and Et3N (97 μL, 0.693 mmol) in CH2Cl2 (7.5 mL) was added over 10 min, then the mixture was stirred for 30 min. The mixture was evaporated and the residue was partitioned between Et2O and aq. 1M HCl. The org. fraction was washed with aq. sat. NaHCO3, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. A sol. of this residue (402 mg, 0.455 mmol) and NaOEt (21% in EtOH, 0.257 mL, 0.683 mmol) in EtOH (2.84 mL) was heated at 80° C. overnight. The mixture was evaporated under reduced pressure, and the residue was dissolved in Et2O. This mixture was washed with aq. 1M HCl, aq. sat. NaHCO3, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC yielded the title compound (300 mg).

Provenance & Evidence