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

HRID 1261506ノート

反応式

HRID 1261506 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
115 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-3db1afcc2a3b4b8b8a261487fa1d00e3
出典データセット
uspto-grants-2013_06
特許番号
US08470866B2

反応ノート

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