Methyl 2,4,6-trimethylbenzeneacetate → 8-Dimethylamino-3-(2,4,6-trimethyl-phenyl)-1-oxa-8-aza-spiro[4.5]decane-2,4-dione

HRID 2367896ノート

反応式

HRID 2367896 の反応式
C[O:2][C:3](=O)[CH2:4][C:5]1[C:10]([CH3:11])=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=1[CH3:13].CO[C:17]([C:19]1([OH:28])[CH2:24][CH2:23][N:22]([N:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]1)=[O:18].CC(C)([O-])C.[K+]>O1CCCC1>[CH3:27][N:25]([CH3:26])[N:22]1[CH2:21][CH2:20][C:19]2([O:28][C:3](=[O:2])[CH:4]([C:5]3[C:10]([CH3:11])=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=3[CH3:13])[C:17]2=[O:18])[CH2:24][CH2:23]1

参加物

5

反応物 3

HCID 13524810Methyl 2,4,6-trimethylbenzeneacetateHCID 23665647Potassium tert-butoxideHCID 672255011-Dimethylamino-4-hydroxy-piperidine-4-carboxylic acid methyl ester

生成物 1

HCID 672263798-Dimethylamino-3-(2,4,6-trimethyl-phenyl)-1-oxa-8-aza-spiro[4.5]decane-2,4-dione収率 9.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a degassed solution of 0.5 g (2,4,6-trimethyl-phenyl)-acetic acid methyl ester and 0.63 g 1-dimethylamino-4-hydroxy-piperidine-4-carboxylic acid methyl ester in 20 ml tetrahydrofuran is added under argon at room temperature 5.72 ml of a 1M potassium tert-butoxide solution in tetrahydrofuran dropwise. The reaction mixture is stirred at room temperature for one hour, and at reflux overnight. The solvent is evaporated, the residue poured into ice/water and the pH adjusted to 5-6 by addition of aqueous 2N hydrochloric acid. The water phase is extracted with diethyl ether, the combined organic layer dried over sodium sulfate, and the solvent evaporated. The crude residue (910 mg) is purified several times by chromatography (normal and reversed phase systems) to yield pure 8-Dimethylamino-3-(2,4,6-trimethyl-phenyl)-1-oxa-8-aza-spiro[4.5]decane-2,4-dione (80 mg) as a solid with mp>200° C. 1H-NMR (DMSO-d6): 6.86 ppm (s, 2H), 2.93 ppm (m, 2H), 2.63 ppm (m, 2H), 2.38 ppm (s, 6H), 2.23 ppm (s, 3H), 2.12 ppm (m, 2H), 2.03 ppm (s, 6H), 1.60 ppm (m, 2H).

後処理

  1. temperatureat reflux overnight
  2. customThe solvent is evaporated
  3. additionthe residue poured into ice/water
  4. additionthe pH adjusted to 5-6 by addition of aqueous 2N hydrochloric acid
  5. extractionThe water phase is extracted with diethyl ether
  6. dry with materialthe combined organic layer dried over sodium sulfate
  7. customthe solvent evaporated
  8. customThe crude residue (910 mg) is purified several times by chromatography (normal and reversed phase systems)

出典と根拠

ORDレコード
ord-c43e963e11744eefbc354d05535cbe47
出典データセット
uspto-grants-2014_04
特許番号
US08703165B2

反応ノート

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