Sodium hydride → (4-Methylmorpholin-3-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate

HRID 2262506ノート

反応式

HRID 2262506 の反応式
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH:5]1[CH2:10][OH:11].[N+](C1C=CC([O:21][C:22]([N:24]2[CH2:29][CH2:28][N:27]([C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[CH2:26][CH2:25]2)=O)=CC=1)([O-])=O.C([O-])(O)=O.[Na+]>C1COCC1>[F:36][C:33]1[CH:32]=[CH:31][C:30]([N:27]2[CH2:26][CH2:25][N:24]([C:22]([O:11][CH2:10][CH:5]3[CH2:6][O:7][CH2:8][CH2:9][N:4]3[CH3:3])=[O:21])[CH2:29][CH2:28]2)=[CH:35][CH:34]=1

参加物

6

反応物 4

HCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 23541157(4-Methylmorpholin-3-yl)methanolHCID 595944824-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester2 回

生成物 1

HCID 42634519(4-Methylmorpholin-3-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate収率 243.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

NaH (60% in oil, prewashed with hexane; 0.91 g, 22.9 mmol) was suspended in anhydrous THF (25 mL) under nitrogen and cooled to 0° C. with stirring. A solution of (4-methyl-morpholin-3-yl)-methanol (1.00 g, 2.62 mmol) in THF (25 mL) was added dropwise. 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 6; 3.16 g, 9.15 mmol) was added and the reaction mixture was stirred overnight at room temperature. A saturated aqueous solution of NaHCO3 (10 mL) was added and the solvents were removed in vacuo. The residue was partitioned between water and EtOAc and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with sat aq NaHCO3 (3×100 mL), dried (MgSO4) and the solvents were removed in vacuo. The residue was purified by flash normal column chromatography (Apollo silica, 40-63 μm, 60 A) eluting with 1% MeOH in DCM to give (4-methylmorpholin-3-yl)methyl 4-(4-fluorophenyl)piperazine-1-carboxylate (2.15 g, 83%) as a white solid.

後処理

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. customthe solvents were removed in vacuo
  3. customThe residue was partitioned between water and EtOAc
  4. extractionthe aqueous phase was extracted with EtOAc
  5. washThe combined organic extracts were washed with sat aq NaHCO3 (3×100 mL)
  6. dry with materialdried (MgSO4)
  7. customthe solvents were removed in vacuo
  8. customThe residue was purified by flash normal column chromatography (Apollo silica, 40-63 μm, 60 A)
  9. washeluting with 1% MeOH in DCM

出典と根拠

ORDレコード
ord-1ef143343584450bade658ce87fe47ad
出典データセット
uspto-grants-2010_12
特許番号
US07851471B2

反応ノート

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