Carbon Dioxide → (3aS,6aR)-hexahydro-1-[(R)-(1-phenylethyl)]-2-oxo-3-benzylthieno[3,4-d]imidazol-4-ylidene pentanoic acid

HRID 232445

反応式

HRID 232445 の反応式
[Mg].Br[CH:3]([CH3:7])[CH:4](Br)[CH3:5].CN(C)CCN(C)C.[C:16]1([C@H:22]([N:24]2[C@H:28]3[CH2:29][S:30][C:31](=O)[C@H:27]3[N:26]([CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:25]2=[O:40])[CH3:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[C:41](=[O:43])=[O:42].Cl>O1CCCC1>[C:16]1([C@H:22]([N:24]2[C@H:28]3[CH2:29][S:30][C:31](=[C:7]([CH2:3][CH2:4][CH3:5])[C:41]([OH:43])=[O:42])[C@H:27]3[N:26]([CH2:33][C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:25]2=[O:40])[CH3:23])[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

参加物

8

反応物 6

HCID 280Carbon DioxideHCID 313Hydrochloric AcidHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 215082,3-DibromobutaneHCID 5462224MagnesiumHCID 11013605(3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno[3,4-d]-imidazol-2,4(3H,3aH)-dione

生成物 1

HCID 86743268(3aS,6aR)-hexahydro-1-[(R)-(1-phenylethyl)]-2-oxo-3-benzylthieno[3,4-d]imidazol-4-ylidene pentanoic acid収率 28%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

0.802 g (33 mmol) of magnesium chips were put into 5 ml of tetrahydrofuran. Then 2.37 g (11 mmol) of dibromobutane in 30 ml tetrahydrofuran was added in 1 hour. The reaction mixture was refluxed for 2 hours, then 2.55 g (22 mmol) of tetramethylethylenediamine was added and refluxed for another hour. To the suspension, cooled to 0° C., was then added 3.52 g (10 mmol) of (3aS,6aR)-1-[(R)-(1-phenylethyl)]-3-benzyl-dihydro-1H-thieno[3,4-d]imidazol-2,4(3H,3aH)-dione in 50 ml of tetrahydrofuran. Then the reaction mixture was stirred for 2 hours at room temperature and then cooled to °0 C. Carbon dioxide gas was introduced in 1 hour at 0° C. and 1 hour at room temperature. The reaction mixture was poured onto a mixture of 85 g of ice and 11.5 ml of conc. hydrochloric acid and then extracted with ethyl acetate. The combined organic phases were washed with water and saturated sodium chloride solution, dried with magnesium sulfate and finally concentrated. 50 mg of p-toluenesulfonic acid was added to the residue, which was then taken up in 170 ml of toluene. The reaction water was refluxed and distilled off by means of a water separator. The remaining toluene solution was concentrated and the resulting oil was chromotographed over silica gel with acetic acid ethyl ester/toluene. 1.22 g (28 percent) of the title product was obtained as a light yellowish oil.

後処理

  1. temperatureThe reaction mixture was refluxed for 2 hours
  2. temperaturerefluxed for another hour
  3. temperaturecooled to °0 C
  4. extractionextracted with ethyl acetate
  5. washThe combined organic phases were washed with water and saturated sodium chloride solution
  6. dry with materialdried with magnesium sulfate
  7. concentrationfinally concentrated
  8. addition50 mg of p-toluenesulfonic acid was added to the residue, which
  9. customThe reaction water
  10. temperaturewas refluxed
  11. distillationdistilled off by means of a water separator
  12. concentrationThe remaining toluene solution was concentrated

出典と根拠

ORDレコード
ord-a5a8d094e06f4aaab7bc1441c144a250
出典データセット
uspto-grants-1989_07
特許番号
US04851540

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