4-[(1-Benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester → HCID 68891896、化合物

HRID 1296389ノート

反応式

HRID 1296389 の反応式
[CH2:1]([Mg]Br)[CH3:2].[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([N:18]([C:20]([CH:22]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:23]2)=O)[CH3:19])[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:5]([O:9][C:10]([N:12]1[CH2:17][CH2:16][CH:15]([N:18]([C:20]2([CH:22]3[CH2:26][CH2:25][N:24]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:23]3)[CH2:2][CH2:1]2)[CH3:19])[CH2:14][CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6]

参加物

5

反応物 2

HCID 694925584-[(1-Benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl esterHCID 178418443HCID 178418443、化合物2 回

生成物 1

HCID 68891896HCID 68891896、化合物収率 38%

試薬・触媒・溶媒 2

HCID 11026Titanium isopropoxide触媒2 回HCID 8028Tetrahydrofuran溶媒4 回

実験手順

The solution of ethylmagnesium bromide (3.0 M in ethyl ether, 2.1 mL, 6.3 mmol) in THF (17.0 mL) was cooled to −78° C. To this solution was added the solution of titanium (IV) isopropoxide (0.76 mL, 2.6 mmol) in THF (1.7 mL) dropwise with the temperature below −70° C. After stirred for three minutes, the solution of 4-[(1-benzyl-pyrrolidine-3-carbonyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester (1.0 g, 2.5 mmol) in THF (1.7 mL) was added. The resulting solution was warmed to room temperature, heated at reflux for one hour and then cooled to 8° C. Ethylmagnesium bromide (3.0M in ethyl ether, 1.8 mL, 5.4 mmol) was added followed by the solution of titanium (IV) isopropoxide (0.66 mL, 2.2 mmol) in THF (1.0 mL) rapidly. The reaction mixture was stirred at room temperature for one hour and partitioned between ethyl acetate and water. The separated organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative thin layer chromatography (60% ethyl acetate in hexane with 0.5% triethylamine) to give pale yellow oil (390 mg, 38%). ESI MS m/z 414.3 (M+H+).

後処理

  1. temperatureheated
  2. temperatureat reflux for one hour
  3. temperaturecooled to 8° C
  4. stirringThe reaction mixture was stirred at room temperature for one hour
  5. custompartitioned between ethyl acetate and water
  6. washThe separated organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by preparative thin layer chromatography (60% ethyl acetate in hexane with 0.5% triethylamine)

出典と根拠

ORDレコード
ord-586eca18e3794382aac50b26f665b8fd
出典データセット
uspto-grants-2007_07
特許番号
US07247634B2

反応ノート

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