Triethylamine → HCID 18177397, compound

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Reaction Steps

In an anhydrous medium, the nitrile obtained in Step E of Example 12 (740 mg; 3.64 mmol) is solubilised in 30 ml of ether; LiAlH4 (1.5 eq; 5.46 mmol; 207 mg) is then added in portions. The mixture is heated at reflux for 3 hours, under argon. After returning to ambient temperature, 210 μl of water, 210 μl of a 15% solution of NaOH, and then 620 μl of water are added in succession. The solution is stirred for 30 minutes at ambient temperature. The salts are filtered off on a frit; the filtrate is dried over MgSO4 and evaporated under reduced pressure. The yellow oil obtained is used immediately in the following Step: in an anhydrous medium, at −10° C., 3-butenoic acid (1.5 eq; 5.43 mmol; 467 mg) and HOBT (1.5 eq; 5.43 mmol; 733 mg). The mixture is stirred, under argon, at −10° C. for 30 minutes. In parallel, the amine is dissolved in 10 ml of distilled CH2Cl2 and placed in the presence of triethylamine (1 eq; 3.62 mmol; 504 μl). The “activated” 3-butenoic acid is then added to the solution of free amine. The reaction medium is left for 2 hours at −10° C., and then for 60 hours at ambient temperature. The mixture is then washed in succession with 1N HCl, with water, with 1N NaOH and with water and dried over MgSO4; the solvent is evaporated under reduced pressure. The residue obtained is purified by flash chromatography on silica gel (eluant: PE/AcOEt (3/7)). The product is obtained in the form of white crystals after washing with ether.

Provenance & Evidence