1,1'-Carbonyldiimidazole → Hydroxy-bis-(3-methoxy-phenyl)-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

HRID 660072ノート

反応式

HRID 660072 の反応式
[OH:1][C:2]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1)([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[CH:7]=1)[C:3]([OH:5])=[O:4].C1N=CN(C(N2C=NC=C2)=O)C=1.[N:34]12[CH2:41][CH2:40][CH:37]([CH2:38][CH2:39]1)[C@@H:36](O)[CH2:35]2>C1COCC1.C(OCC)(=O)C>[N:34]12[CH2:41][CH2:40][CH:37]([CH2:38][CH2:39]1)[C@@H:36]([O:4][C:3](=[O:5])[C:2]([OH:1])([C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH3:13])[CH:7]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH3:21])[CH:15]=1)[CH2:35]2

参加物

6

反応物 3

HCID 682631,1'-CarbonyldiimidazoleHCID 914043-Quinuclidinol, (-)-HCID 585026Hydroxy-bis-(3-methoxyphenyl)acetic acid2 回

生成物 1

HCID 86627867Hydroxy-bis-(3-methoxy-phenyl)-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of hydroxy-bis-(3-methoxy-phenyl)-acetic acid (Intermediate J) (1.384 g, 4.8 mmol) in dry THF (2.0 ml) is added CDI (0.870 g, 5.3 mmol) and the mixture is heated to reflux for 90 minutes. (R)-1-aza-bicyclo[2.2.2]octan-3-ol (0.67 g, 5.3 mmol) is then added. After refluxing for 16 hours, the reaction mixture is diluted with ethyl acetate and washed with water. The organic layer is then extracted with 2M HCl and the aqueous portion is treated with potassium carbonate to basify the solution. The aqueous portion is re-extracted with ethyl acetate. The organic portions are combined, dried over MgSO4 and concentrated in vacuo to yield a crude residue which is purified using C-18 reverse phase column chromatography (eluent: water-acetonitrile), to afford the titled compound.

後処理

  1. temperaturethe mixture is heated
  2. temperatureto reflux for 90 minutes
  3. temperatureAfter refluxing for 16 hours
  4. washwashed with water
  5. extractionThe organic layer is then extracted with 2M HCl
  6. additionthe aqueous portion is treated with potassium carbonate
  7. extractionThe aqueous portion is re-extracted with ethyl acetate
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customto yield a crude residue which
  11. customis purified

出典と根拠

ORDレコード
ord-98ff7986f7d846c1a0ebaac6d465d72c
出典データセット
uspto-grants-2011_12
特許番号
US08084463B2

反応ノート

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