Sodium hydride → [(2R)-4-methylmorpholin-2-yl]methyl 4-(4-fluorophenyl)piperazine-1-carboxylate

HRID 2262494ノート

反応式

HRID 2262494 の反応式
[CH3:1][N:2]1[CH2:7][CH2:6][O:5][C@@H:4]([CH2:8][OH:9])[CH2:3]1.[H-].[Na+].[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>C1COCC1>[F:36][C:33]1[CH:32]=[CH:31][C:30]([N:27]2[CH2:26][CH2:25][N:24]([C:22]([O:9][CH2:8][C@@H:4]3[O:5][CH2:6][CH2:7][N:2]([CH3:1])[CH2:3]3)=[O:21])[CH2:29][CH2:28]2)=[CH:35][CH:34]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 40152301(R)-4-Methyl-2-(hydroxymethyl)morpholine2 回HCID 595944824-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester2 回

生成物 1

HCID 42634187[(2R)-4-methylmorpholin-2-yl]methyl 4-(4-fluorophenyl)piperazine-1-carboxylate収率 39%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(R)-(4-Methyl-morpholin-2-yl)-methanol (Intermediate 11; 100 mg, 0.76 mmol) was added to a suspension of NaH (60% dispersion in oil; 90.0 mg, 2.28 mmol) in anhydrous THF (7 mL) and stirred under nitrogen for 30 min. 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4-nitrophenyl ester (Intermediate 6; 314 mg, 0.91 mmol) was added and the reaction mixture was stirred at room temperature for 48 h. The reaction mixture was filtered through celite and the solid washed with THF (10 mL). The filtrates were combined and the solvent removed in vacuo. The residue was purified by column chromatography (normal phase silica, 5 g Isolute-Si column, gradient 1-5% MeOH in DCM) and then reverse phase HPLC (YMC ODS-A 100×20 mm, 5 μm, 25 mL/min, gradient 20% to 100% (over 7 min) then 100% (3 min) MeOH in 10% MeOH/water). The pure product was taken up in DCM (5 mL), filtered, and dried in vacuo to give [(2R)-4-methylmorpholin-2-yl]methyl 4-(4-fluorophenyl)piperazine-1-carboxylate (100 mg, 28%) as a colourless gum.

後処理

  1. stirringthe reaction mixture was stirred at room temperature for 48 h
  2. filtrationThe reaction mixture was filtered through celite
  3. washthe solid washed with THF (10 mL)
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by column chromatography (normal phase silica, 5 g Isolute-Si column, gradient 1-5% MeOH in DCM)
  6. customYMC ODS-A 100×20 mm, 5 μm, 25 mL/min, gradient 20% to 100% (over 7 min)
  7. custom100% (3 min) MeOH in 10% MeOH/water
  8. filtrationfiltered
  9. customdried in vacuo

出典と根拠

ORDレコード
ord-c2269a9beb7d4bdaa17a65023e6198ce
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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