Water → 1'-benzyl-5-methyl-3H-spiro[1-benzofuran-2,4'-piperidine]

HRID 270038ノート

反応式

HRID 270038 の反応式
[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][C:13]([CH2:17][C:18]2[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=2F)([OH:16])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CN(C=O)C.O>C1(C)C=CC=CC=1>[CH2:3]([N:10]1[CH2:15][CH2:14][C:13]2([CH2:17][C:18]3[CH:23]=[C:22]([CH3:24])[CH:21]=[CH:20][C:19]=3[O:16]2)[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

参加物

6

反応物 4

HCID 962WaterHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 598336351-Benzyl-4-(2-fluoro-5-methylbenzyl)piperidin-4-ol

生成物 1

HCID 598336331'-benzyl-5-methyl-3H-spiro[1-benzofuran-2,4'-piperidine]収率 41%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
110 °C

実験手順

To a suspension of NaH (55% in mineral oil, 200 mg, 5 mmol) in toluene (10 mL) was slowly added a solution of crude 1-benzyl-4-(2-fluoro-5-methylbenzyl)piperidin-4-ol in toluene (15 mL). After addition was completed, the reaction mixture was heated to 110° C. and stirred for 5 min. DMF (9 mL) was added and stirring was continued at reflux temperature for 10 h. The reaction mixture was cooled to room temperature, poured into water (50 ml), and extracted with ethyl acetate (2×25 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash chromatography (ethyl acetate/n-heptane) to give the subtitle compound (240 mg, 41%).

後処理

  1. additionAfter addition
  2. stirringstirring
  3. temperatureat reflux temperature for 10 h
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionextracted with ethyl acetate (2×25 ml)
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel flash chromatography (ethyl acetate/n-heptane)

出典と根拠

ORDレコード
ord-260f62b0aab84857b4fdc4e95d4293a3
出典データセット
uspto-grants-2008_11
特許番号
US07449475B2

反応ノート

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