3-(Bromomethyl)-5-methylisoxazole → Ammonium Hydroxide

HRID 1630768ノート

反応式

HRID 1630768 の反応式
Cl.[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:29][C:30]1[CH:34]=[C:33]([CH3:35])[O:32][N:31]=1>C1COCC1>[NH4+:5].[OH-:32].[CH3:2][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:29][C:30]2[CH:34]=[C:33]([CH3:35])[O:32][N:31]=2)[C:4]=1[C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1

参加物

6

反応物 3

HCID 27763043-(Bromomethyl)-5-methylisoxazoleHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539613-Methyl-2-(3-pyridyl)indole hydrochloride

生成物 2

HCID 14923Ammonium Hydroxide収率 0.1%HCID 445541373-methyl-1-(5-methyl-isoxazol-3-ylmethyl)-2-pyridin-3-yl-1H-indole

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

A flask is charged with 3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 1, 0.100 g, 0.408 mmol) in THF (2.5 mL) and cooled to 0° C. KHMDS (0.5 M in toluene, 1.8 mL, 0.898 mmol) is added and the mixture is stirred at room temperature for 30 min, followed by addition of 3-bromomethyl-5-methyl-isoxazole (0.144 g, 0.817 mmol). The reaction mixture is stirred for 0.5 h, then quenched with saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by reverse phase HPLC with Xbridge Shield RP18 column and a 0.1% aqueous NH4OH in acetonitrile gradient to afford 3-methyl-1-(5-methyl-isoxazol-3-ylmethyl)-2-pyridin-3-yl-1H-indole product as a colorless oil. The oil is dissolved in diethyl ether and few drops of concentrated HCl are added. The volatiles are removed in vacuo and the reside is lyophilized to afford the product as a yellow solid. 1H NMR (400 MHz, MeOD) δ ppm (HCl salt) 2.30 (s, 3H), 2.31 (s, 3H), 5.30 (s, 2H), 5.67 (s, 1H), 7.18 (t, J=8.0 Hz, 1H), 7.27 (ddd, J=7.6, 1.1 Hz, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.56-7.69 (m, 2H), 7.99 (dt, J=8.0, 1.9, 1.8 Hz, 1H), 8.56-8.68 (m, 2H). HRMS (ESI) m/z 304.1440 [(M+H)+ Calcd for C19H18N3O, 304.1450].

後処理

  1. stirringThe reaction mixture is stirred for 0.5 h
  2. customquenched with saturated ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by reverse phase HPLC with Xbridge Shield RP18 column

出典と根拠

ORDレコード
ord-96c85a61f7ca47b7b811237902cc5226
出典データセット
uspto-grants-2014_07
特許番号
US08791141B2

反応ノート

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