Hexane → Tert-butyl 4-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}methylamino)benzoate

HRID 967780ノート

反応式

HRID 967780 の反応式
CCCCCC.C([Li])CCC.[CH3:12][NH:13][C:14]1[CH:26]=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:16][CH:15]=1.[C:27]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][N:37]2[CH2:44][CH2:43][C:40]3([CH2:42][O:41]3)[CH2:39][CH2:38]2)=[CH:31][CH:30]=1)#[N:28]>O.O1CCCC1>[C:27]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][N:37]2[CH2:44][CH2:43][C:40]([CH2:42][N:13]([CH3:12])[C:14]3[CH:15]=[CH:16][C:17]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])=[CH:25][CH:26]=3)([OH:41])[CH2:39][CH2:38]2)=[CH:31][CH:30]=1)#[N:28]

参加物

7

反応物 4

HCID 8058HexaneHCID 22291264tert-Butyl 4-(methylamino)benzoateHCID 858197211-[2-(4-Cyanophenyl)ethyl]piperidin-4-spiro-2'-oxiraneHCID 178418339Butyllithium

生成物 1

HCID 22930217Tert-butyl 4-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}methylamino)benzoate収率 49.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A hexane solution of n-butyllithium (1.57M; 2.68 mL) was added dropwise to an anhydrous tetrahydrofuran solution (4.22 mL) of the compound (874 mg) obtained in Step 1 at the internal temperature of below 5° C. and the mixture was stirred under cooling with ice-water for one hour. To the mixture was added dropwise an anhydrous tetrahydrofuran solution (4.22 mL) of the compound (1.02 g) obtained in Step 3 of Example 1 at the internal temperature of below 5° C. over thirty minutes, stirred at the same temperature for one hour and further at room temperature for fifty two hours. To the solution added water (40 mL) under cooling with ice-water and the residue was extracted with ethyl acetate. After the organic layer was washed with brine and dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (Chromatorex NH™)(eluent; hexane:ethyl acetate=7:3 to 1:1) to obtain the titled compound (940 mg) as powder.

後処理

  1. stirringstirred at the same temperature for one hour and further at room temperature for fifty two hours
  2. extractionthe residue was extracted with ethyl acetate
  3. washAfter the organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (Chromatorex NH™)(eluent; hexane:ethyl acetate=7:3 to 1:1)

出典と根拠

ORDレコード
ord-345b9e7aaf85473fb9d57b2dfe08d1b0
出典データセット
uspto-grants-2005_10
特許番号
US06956046B2

反応ノート

読み込み中…