Triethylamine → HCID 68745035, compound

HRID 1714811Notes

Reaction equation

HRID 1714811 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:18][CH2:17][CH2:16][C@H:12]1[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1C=CN=C1)([N:21]1[CH:25]=[CH:24]N=C1)=O.Cl.C[O:33]C(=O)CN.C(N(CC)CC)C>O1CCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][C:13](=[O:15])[N:21]2[CH2:25][CH2:24][CH2:16][C@H:17]2[C:18]1=[O:33])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 101987Benzyloxycarbonyl-L-prolineHCID 122755Glycine methyl ester hydrochloride

Product 1

HCID 68745035HCID 68745035, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In 150 ml of tetrahydrofuran, 12.5 g of N-benzyloxycarbonyl-L-proline and 8.9 g of carbonyldiimidazole were dissolved and stirred for 30 minutes. Then 6.9 g of glycine methyl ester hydrochloride and 5.6 g of triethylamine were added to the solution and stirred for an overnight at room temperature. The solution was concentrated, and ethyl acetate was added, followed by washing with saturated aqueous sodium hydrogencarbonate solution, 10% aqueous citric acid and saturated brine, drying over anhydrous magnesium sulfate and concentration. The residue was dissolved in 100 ml of methanol, to which solution 2.0 g of 10% palladium-on-carbon was added and stirred for an overnight in gaseous hydrogen current. Filtering the catalyst off, the filtrate was concentrated. This residue was dissolved in 100 ml of methanol and following addition of triethylamine, the solution was heated under reflux for 14 hours. After concentration, a suitable amount of 2-propanol was added to the residue and the precipitated crystals were recovered by filtration and dried to provide 6.48 g (84%) of (8aS)-2-benzyloxycarbonylhexahydropyrrolo[1,2-a]pyrazin-1,4-dione. In 40 ml of tetrahydrofuran, 4.0 g of this product was dissolved and the solution was dropped into a suspension of 5.9 g of lithium aluminium hydride in 60 ml of tetrahydrofuran, followed by 14 hours' heating under reflux. The solution was cooled with ice, and excessive lithium aluminium hydride therein was decomposed by addition of saturated aqueous sodium hydrogencarbonate solution. After addition of benzyloxycarbonyl chloride, the solution was stirred for an hour under cooling with ice and for further 2 hours at room temperature, followed by extraction with chloroform, washing with saturated brine, drying over anhydrous magnesium sulfate and concentration. The residue was purified on silica gel column chromatography (chloroform:methanol=25:1) to provide 2.77 g (41%) of (8aS)-2-benzyloxycarbonyloctahydropyrrolo[1,2-a]pyrazine.

Workup

  1. stirringstirred for an overnight at room temperature
  2. concentrationThe solution was concentrated
  3. additionethyl acetate was added
  4. washby washing with saturated aqueous sodium hydrogencarbonate solution, 10% aqueous citric acid and saturated brine
  5. dry with materialdrying over anhydrous magnesium sulfate and concentration
  6. dissolutionThe residue was dissolved in 100 ml of methanol, to which solution 2.0 g of 10% palladium-on-carbon
  7. additionwas added
  8. stirringstirred for an overnight in gaseous hydrogen current
  9. filtrationFiltering the catalyst off, the filtrate
  10. concentrationwas concentrated
  11. dissolutionThis residue was dissolved in 100 ml of methanol
  12. additionaddition of triethylamine
  13. temperaturethe solution was heated
  14. temperatureunder reflux for 14 hours
  15. concentrationAfter concentration
  16. additiona suitable amount of 2-propanol was added to the residue
  17. filtrationthe precipitated crystals were recovered by filtration
  18. customdried

Sources & evidence

ORD record
ord-7dd8d8ef905f47f3a5263bd186f9e23c
Source dataset
uspto-grants-2010_09
Patent number
US07799775B2

Reaction notes

Loading…