2-Butene, 1-bromo-3-methyl- → (S)-4-Methyl-2-(3-methyl-but-2-enylamino)-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

HRID 990332Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 990332
[ClH:1].[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:21])[C@@H:15]([NH2:20])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.Br[CH2:39][CH:40]=[C:41]([CH3:43])[CH3:42]>C1COCC1>[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:21])[C@@H:15]([NH:20][CH2:39][CH:40]=[C:41]([CH3:43])[CH3:42])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:7][CH:8]=1

Komponenten

5

Edukt 3

HCID 700922-Butene, 1-bromo-3-methyl-HCID 81531DiisopropylethylamineHCID 86758543(S)-2-Amino-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

Produkt 1

HCID 9912978(S)-4-Methyl-2-(3-methyl-but-2-enylamino)-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochlorideAusbeute 36 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution of (S)-2-amino-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride (0.36 g, 0.88 mmol, Example 7) in THF (15 mL) were added, in succession, N,N-diisopropylethylamine (0.30 mL, 1.7 mmol) and 1-bromo-3-methyl-2-butene (0.10 mL, 0.87 mmol) at ambient temperature under nitrogen atmosphere. The resulting reaction mixture was stirred for 12 hours at that temperature, 16 hours at 50° C., cooled to ambient temperature, and concentrated in vacuo. The desired product was purified by flash chromatography (50% EtOAc in hexanes) and was dissolved in 10 mL of ethyl ether. To this solution was added saturated HCl solution in ethyl ether until no more white precipitate formed. Filtration and drying overnight under vacuum afforded 0.14 g (36%) of the titled compound as a yellow foam; mp 58-72° C. APCI-MS m/z 443.3 (MH+).

Aufarbeitung

  1. customThe resulting reaction mixture
  2. temperaturecooled to ambient temperature
  3. concentrationconcentrated in vacuo
  4. customThe desired product was purified by flash chromatography (50% EtOAc in hexanes)
  5. dissolutionwas dissolved in 10 mL of ethyl ether
  6. additionTo this solution was added saturated HCl solution in ethyl ether until no more white precipitate
  7. customformed
  8. filtrationFiltration
  9. customdrying overnight under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-e93e117dde3242fc8cdb6042b746e2df
Quelldatensatz
uspto-grants-2002_10
Patentnummer
US06458781B1

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