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Potassium Carbonate → 7-(2-{1-[2-(4-Cyanophenoxy)ethyl]-3-methylureido}ethyl)-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester

HRID 899152
ノート
印刷プレビュー

反応式

HRID 899152 の反応式
[C:1]([C:3]1[CH:29]=[CH:28][C:6]([O:7][CH2:8][CH2:9][N:10]([CH2:15][CH2:16]OS(C2C=CC(C)=CC=2)(=O)=O)[C:11]([NH:13][CH3:14])=[O:12])=[CH:5][CH:4]=1)#[N:2].[C:30]([O:34][C:35]([N:37]1[CH2:44][CH:43]2[O:45][CH:39]([CH2:40][NH:41][CH2:42]2)[CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[C:30]([O:34][C:35]([N:37]1[CH2:38][CH:39]2[O:45][CH:43]([CH2:42][N:41]([CH2:16][CH2:15][N:10]([CH2:9][CH2:8][O:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:29][CH:28]=3)[C:11]([NH:13][CH3:14])=[O:12])[CH2:40]2)[CH2:44]1)=[O:36])([CH3:33])([CH3:31])[CH3:32]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 185404123-Boc-9-oxa-3,7-diazabicyclo[3.3.1]nonaneHCID 86616243Toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]-3-methylureido}ethyl ester

生成物 1

HCID 690680227-(2-{1-[2-(4-Cyanophenoxy)ethyl]-3-methylureido}ethyl)-9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester収率 60.1%

試薬・触媒・溶媒 2

HCID 962
Water
溶媒
HCID 6342Acetonitrile溶媒

反応条件

温度
45 °C

実験手順

A mixture of toluene-4-sulfonic acid 2-{1-[2-(4-cyanophenoxy)ethyl]-3-methylureido}ethyl ester (1.35 g, 3.233 mmol; see Preparation I above), 9-oxa-3,7-diaza-bicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester (1.48 g, 6.466 mmol; see WO 01/28992) and potassium carbonate (1.34 g, 9.7 mmol) in dry acetonitrile (15 mL) was stirred at 45° C. for 24 h. The reaction mixture was diluted with 20 mL water and extracted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. Solvent evaporation under reduced pressure followed by column chromatography over silica gel (using 2-2.5% methanol in dichloromethane) and further purification by preparative HPLC yielded 920 mg of the title compound as a white solid.

後処理

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with water, brine
  3. dry with materialdried over sodium sulfate
  4. customSolvent evaporation under reduced pressure
  5. customfollowed by column chromatography over silica gel (using 2-2.5% methanol in dichloromethane) and further purification by preparative HPLC

出典と根拠

ORDレコード
ord-e442157e8ce74073ab671e05c8bde9ef
出典データセット
uspto-grants-2008_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07354917B2

反応ノート

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