Triethylamine → HCID 18177397, compound

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.

1. temperatureThe mixture is heated
2. temperatureat reflux for 3 hours, under argon
3. customAfter returning to ambient temperature
4. filtrationThe salts are filtered off on a frit
5. dry with materialthe filtrate is dried over MgSO4
6. customevaporated under reduced pressure
7. customThe yellow oil obtained
8. customat −10° C.
9. stirringThe mixture is stirred, under argon, at −10° C. for 30 minutes
10. waitThe reaction medium is left for 2 hours at −10° C.
11. waitfor 60 hours at ambient temperature
12. washThe mixture is then washed in succession with 1N HCl, with water, with 1N NaOH and with water
13. dry with materialdried over MgSO4
14. customthe solvent is evaporated under reduced pressure
15. customThe residue obtained
16. customis purified by flash chromatography on silica gel (eluant: PE/AcOEt (3/7))
17. customThe product is obtained in the form of white crystals
18. washafter washing with ether

ORD record

ord-624e25518e0a447e8488fc1be9194d36

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06602903B2