Ethyl orthopropionate → HCID 10224328, compound

HRID 431015Notes

Reaction equation

HRID 431015 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:10][CH2:9][C@H:8]([CH2:11]OS(C3C=CC(C)=CC=3)(=O)=O)[O:7][C:6]=2[C:23]=1[CH:24]=[N:25]O.[NH:27]1[CH2:32][CH:31]=[C:30]([C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[NH:35][CH:34]=2)[CH2:29][CH2:28]1.C(=O)(O)[O-].[Na+].[C:47](OCC)(OCC)(OCC)[CH2:48][CH3:49]>>[NH:35]1[C:36]2[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:33]([C:30]2[CH2:29][CH2:28][N:27]([CH2:11][CH:8]3[O:7][C:6]4=[C:23]5[C:2](=[CH:3][CH:4]=[C:5]4[O:10][CH2:9]3)[N:1]=[C:47]([CH2:48][CH3:49])[N:25]=[CH:24]5)[CH2:32][CH:31]=2)=[CH:34]1

Participants

5

Reactant 4

HCID 66995Ethyl orthopropionateHCID 516892Sodium BicarbonateHCID 27610233-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indoleHCID 86586526HCID 86586526, compound

Product 1

HCID 10224328HCID 10224328, compound

Procedure

Toluene-4-sulfonic acid (2R)-7-amino-8-(hydroximino-methyl)2,3-dihydrobenzo[1,4]dioxin-2-ylmethyl ester (1.0 g, mmole) was suspended in triethyl orthopropionate (20 mL) and the mixture refluxed under nitrogen for 18 hours. The reaction mixture was cooled and the solvent evaporated under vacuum. The residue was dissolved in methylene chloride, the solution washed with saturated sodium chloride solution, dried over magnesium sulfate and the solvent evaporated to a gum (1.5 g). This residue was dried under vacuum and dissolved in a mixture of DMF/THF 1:1 v/v (100 mL). 3-(1,2,3,6-Tetrahydro-4-pyridinyl)-1H-indole (1.2 g, 6 mmole) and sodium bicarbonate (3.0 g) were added and the mixture refluxed under nitrogen for 20 hours. The reaction mixture was cooled, and the solvent evaporated under vacuum. The residue was partitioned between methylene chloride and water. The layers were separated. The organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate and the solvent removed under vacuum. The crude oil obtained (2.0 g) was chromatographed on silica gel using 2% methanol in chloroform, followed by 3% methanol in chloroform as eluants to give the (S)-enantiomer of the title compound (52 mg), m.p. 203-211° C.

Workup

  1. temperaturethe mixture refluxed under nitrogen for 18 hours
  2. temperatureThe reaction mixture was cooled
  3. customthe solvent evaporated under vacuum
  4. dissolutionThe residue was dissolved in methylene chloride
  5. washthe solution washed with saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent evaporated to a gum (1.5 g)
  8. customThis residue was dried under vacuum
  9. dissolutiondissolved in a mixture of DMF/THF 1:1 v/v (100 mL)
  10. temperaturethe mixture refluxed under nitrogen for 20 hours
  11. temperatureThe reaction mixture was cooled
  12. customthe solvent evaporated under vacuum
  13. customThe residue was partitioned between methylene chloride and water
  14. customThe layers were separated
  15. washThe organic phase was washed with water and saturated sodium chloride solution
  16. dry with materialdried over magnesium sulfate
  17. customthe solvent removed under vacuum
  18. customThe crude oil obtained (2.0 g)
  19. customwas chromatographed on silica gel using 2% methanol in chloroform

Sources & evidence

ORD record
ord-c77e72d14fb7419ebdacce903d70aec7
Source dataset
uspto-grants-2003_12
Patent number
US06656947B2

Reaction notes

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