Triethylamine → (S)-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyric acid methyl ester

HRID 2365740

Reaktionsgleichung

Reaktionsgleichung von HRID 2365740
Cl.[CH3:2][O:3][C:4](=[O:11])[C@@H:5]([NH2:10])[CH2:6][CH2:7][S:8][CH3:9].C[O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[C:16]=1[CH2:25]Br.C(N(CC)CC)C>C(#N)C>[CH3:2][O:3][C:4](=[O:11])[C@@H:5]([N:10]1[CH2:25][C:16]2[C:15](=[CH:20][CH:19]=[CH:18][C:17]=2[C:21]([F:24])([F:22])[F:23])[C:14]1=[O:13])[CH2:6][CH2:7][S:8][CH3:9]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 17837607Methyl 2-(bromomethyl)-3-(trifluoromethyl)benzoate

Produkt 1

HCID 70945579(S)-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyric acid methyl esterAusbeute 40 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
115 °C

Versuchsvorschrift

A mixture of (S)-2-amino-4-methylsulfanyl-butyric acid methyl ester hydrochloride (Aldrich, 199 mg, 1 mmol) and 2-bromomethyl-3-trifluoromethyl-benzoic acid methyl ester (prepared as in Example 1, 297 mg, 1 mmol) in acetonitrile (5 mL) and triethylamine (280 μL, 2 mmol) was placed in a microwave reaction vessel and sealed. The reaction mixture was then placed in a microwave reactor and heated at 115° C. for 15 min. After this time, the reaction mixture was cooled and concentrated with silica gel (2 g) in vacuo. The silica gel with absorbed material was placed in a SIM and purified via Biotage flash column chromatography (40 S silica gel column, 25% ethyl acetate/hexanes) to afford (S)-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyric acid methyl ester (137 mg, 40%) as a colorless viscous oil: HR-ES(+) m/e calcd for C15H16NO3SF3 [M+H]+ 348.0876, observed 348.0874; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.07 (d, J=7.46 Hz, 1H), 7.83 (d, J=7.67 Hz, 1H), 7.64 (t, J=7.67 Hz, 1H), 5.25 (dd, J=4.69, 10.44 Hz, 1H), 4.79 (d, J=17.47 Hz, 1H), 4.53 (d, J=17.47 Hz, 1H), 3.77 (s, 3H), 2.38-2.62 (m, 3H), 2.16-2.31 (m, 1H), 2.13 (s, 3H).

Aufarbeitung

  1. customwas placed in a microwave reaction vessel
  2. customsealed
  3. customThe reaction mixture was then placed in a microwave reactor
  4. temperatureAfter this time, the reaction mixture was cooled
  5. concentrationconcentrated with silica gel (2 g) in vacuo
  6. custompurified via Biotage flash column chromatography (40 S silica gel column, 25% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-78159849806a4cf08d5e73ef5026d0ea
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697705B2

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