Ethylene Glycol → (-)-4-[4-[2-(Isochroman-1-yl)ethyl]piperazin-1-yl]benzamide

HRID 368845

反応式

HRID 368845 の反応式
CN([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6]N=1)C.[CH:10](N(C(C)C)CC)([CH3:12])[CH3:11].[CH3:19]S(Cl)(=O)=O.[N:24]1([C:30]2[CH:38]=[CH:37][C:33]([C:34]([NH2:36])=[O:35])=[CH:32][CH:31]=2)[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.[CH2:39]([OH:42])[CH2:40]O>O.C1COCC1>[CH:39]1([CH2:40][CH2:19][N:27]2[CH2:26][CH2:25][N:24]([C:30]3[CH:31]=[CH:32][C:33]([C:34]([NH2:36])=[O:35])=[CH:37][CH:38]=3)[CH2:29][CH2:28]2)[C:12]2[C:8](=[CH:9][CH:4]=[CH:11][CH:10]=2)[CH2:7][CH2:6][O:42]1

参加物

8

反応物 5

HCID 174Ethylene GlycolHCID 218852-DimethylaminopyridineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 111065094-(1-Piperazinyl)benzamide

生成物 1

HCID 10270210(-)-4-[4-[2-(Isochroman-1-yl)ethyl]piperazin-1-yl]benzamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

Borane-methyl sulfide (10.5 ml) in THF is added to an ice-cooled solution of (-)-(isochroman-1-yl)acetic acid (LXI, EXAMPLE 45--Step 3, 7.08 g, 36.8 mmol). After stirring for 20 min at 0°, the ice bath is removed and the solution is stirred at 20-25° for another 1.7 hr. The reaction flask is then placed in an ice-water bath and methanol is added slowly until no further gas evolution occurs. The solvents are then removed under reduced pressure and methanol is again added and removed a second and third time. The residue is partitioned between dichloromethane, aqueous sodium bicarbonate and saline. The organic phase is separated, dried over sodium sulfate and concentrated to give (-)-2-(isochroman-1-yl)ethanol (LXXIX). This material is added to dimethylaminopyridine (0.22 g, 1.8 mmol), diisopropylethylamine (16.0 ml, 92 mmol) and THF (60 ml). The mixture is cooled in an ice-water bath and methanesulfonyl chloride (3.4 ml, 44.2 mmol) is added dropwise over several minutes. After stirring for 55 min at 0°, 4-(piperazin-1-yl)benzamide (IV, EXAMPLE 47 Step 1, 9.06 g, 44.2 mmol) and ethylene glycol (60 ml) are added. The mixture is heated at 80° overnight and then water is added and the resulting solid is collected and washed with water and toluene. After drying, the solid is passed through silica gel using methanol/dichloromethane (4/96) to give (-)-4-[4-[2-(isochroman-1-yl)ethyl]piperazin-1-yl]benzamide, MS (m/z) 365; IR (mineral oil) 1610, 1239, 1643, 1112, 1622 cm-1.

後処理

  1. temperatureThe mixture is cooled in an ice-water bath
  2. temperatureThe mixture is heated at 80° overnight
  3. customthe resulting solid is collected
  4. washwashed with water and toluene
  5. customAfter drying

出典と根拠

ORDレコード
ord-b28812d5288a485eacc0574abdc60c51
出典データセット
uspto-grants-2000_10
特許番号
US06133446

関連ノート

読み込み中…