Water → 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxy-N,N-bis(1-methylethyl)-benzamide

HRID 376067ノート

反応式

HRID 376067 の反応式
[CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].CN(C)CCN.[C:14]([C:16]1[CH:39]=[CH:38][C:19]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27]2[CH:35]=[CH:34][C:30]([C:31](O)=[O:32])=[CH:29][C:28]=2[O:36][CH3:37])=[CH:18][CH:17]=1)#[N:15].O>ClCCl>[C:14]([C:16]1[CH:17]=[CH:18][C:19]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27]2[CH:35]=[CH:34][C:30]([C:31]([N:4]([CH:5]([CH3:7])[CH3:6])[CH:1]([CH3:3])[CH3:2])=[O:32])=[CH:29][C:28]=2[O:36][CH3:37])=[CH:38][CH:39]=1)#[N:15]

参加物

6

反応物 4

HCID 962WaterHCID 7912DiisopropylamineHCID 66053N,N-DimethylethylenediamineHCID 189917354-[5-(4-Cyanophenoxy)pentoxy]3-methoxybenzoic acid

生成物 1

HCID 189916954-[5-(4-cyanophenoxy)pentoxy]-3-methoxy-N,N-bis(1-methylethyl)-benzamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
5 °C

実験手順

4-[5-(4-cyanophenoxy)pentoxy]-3-methoxybenzoic acid (3600 g, 10.13 mol) is suspended in dichloromethane (36 L) and to this is added thionyl chloride (1345 g, 11.30 mol) dropwise over 20 minutes followed by dimethylformamide (74.4 g, 10.0 mol). The reaction mixture is stirred at room temperature for 21 hours; after 6 hours a complete solution is obtained. The solution is concentrated in vacuo (50° C., 3 mm Hg) to give 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxybenzoyl chloride as a solid, which is then redissolved in dichloromethane (36 L) without further purification and cooled to 5° C. with an ice bath. Diisopropylamine (3077 g, 30.40 mol) is added dropwise over a period of 1 hour. The reaction mixture is stirred at 20° C. for 3 hours and then, N,N-dimethylethylenediamine (80.3 g, 0.91 mol) is added. The reaction is followed by TLC (2:1 ethyl acetate/hexanes, silica plates) until no more byproduct (bis-anhydride of 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxybenzoic acid) is detected. The reaction mixture is then stirred overnight at room temperature. Water (18 L) is added, stirred and the layers separated. The organic layer is washed with hydrochloric acid (1.0N, 23 L), water (18 L), ammonium hydroxide (0.5N, 2×23 L), water (18 L) and brine solution (18 L). The separated dichloromethane solution is dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo (50° C., 3 mm Hg) to give 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxy-N,N-bis(1-methylethyl)-benzamide as a solid. The solid is dissolved in 2 B ethanol (21.5 L) by warming and to the solution is added water (8.6 L). The product is allowed to crystallize overnight in an ice bath. The product is filtered, washed with EtOH/H2O (5:2, 2×2 L) and dried in vacuo (54° C., 3 mm Hg) to give 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxy-N,N-bis(1-methylethyl)-benzamide, mp 90°-92° C. HPLC indicates a purity of >99.7%.

後処理

  1. stirringThe reaction mixture is then stirred overnight at room temperature
  2. stirringstirred
  3. customthe layers separated
  4. washThe organic layer is washed with hydrochloric acid (1.0N, 23 L), water (18 L), ammonium hydroxide (0.5N, 2×23 L), water (18 L) and brine solution (18 L)
  5. dry with materialThe separated dichloromethane solution is dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo (50° C., 3 mm Hg)

出典と根拠

ORDレコード
ord-f265e93ed6d249a88d490ccfd97dc382
出典データセット
uspto-grants-1996_01
特許番号
US05488160

反応ノート

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