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

HRID 1197307Notes

Reaction equation

HRID 1197307 reaction equation
[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

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-4d178088fada414ba7f62052fcde0ad3
Source dataset
uspto-grants-1992_05
Patent number
US05117003

Reaction notes

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