Triethyl orthoacetate → HCID 10296188, compound

HRID 431014Notes

Reaction equation

HRID 431014 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][OH:26].[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)[CH3:48]>C1COCC1.CN(C=O)C>[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]([CH3:48])[N+:25]([O-:26])=[CH:24]5)[CH2:32][CH:31]=2)=[CH:34]1

Participants

6

Reactant 4

HCID 66221Triethyl orthoacetateHCID 516892Sodium BicarbonateHCID 27610233-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indoleHCID 86586526HCID 86586526, compound

Product 1

HCID 10296188HCID 10296188, compound

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

Toluene-4-sulfonic acid (2R)-7-amino-8-(hydroximino-methyl)-2,3-dihydro-1,4-benzodioxin-2-ylmethyl ester (1.0 g, 2.6 mmole) was suspended in triethyl orthoacetate (20 mL) and the mixture refluxed under nitrogen for two hours. The reaction mixture was cooled, and the solvent evaporated under vacuum. The crude residue (1.5 g) was dissolved in a mixture of THF/DMF 1:1 v/v (25 mL) and 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H-indol (1.5 g, 7.5 mmole) and sodium bicarbonate (1.5 g) added. The mixture was refluxed under nitrogen for 20 hours. The reaction mixture was cooled, and the solvent evaporated. 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 evaporated under vacuum. The crude residual oil (2.7 g) was chromatographed on silica gel using 1% methanol in chloroform, followed by 2% and 3% methanol in chloroform as eluants, to give the (S)-enantiomer of the title compound as a yellow solid (40 mg), m.p. 118-192° C.

Workup

  1. temperaturethe mixture refluxed under nitrogen for two hours
  2. temperatureThe reaction mixture was cooled
  3. customthe solvent evaporated under vacuum
  4. additionadded
  5. temperatureThe mixture was refluxed under nitrogen for 20 hours
  6. temperatureThe reaction mixture was cooled
  7. customthe solvent evaporated
  8. customThe residue was partitioned between methylene chloride and water
  9. customThe layers were separated
  10. washThe organic phase was washed with water and saturated sodium chloride solution
  11. dry with materialdried over magnesium sulfate
  12. customthe solvent evaporated under vacuum
  13. customThe crude residual oil (2.7 g) was chromatographed on silica gel using 1% methanol in chloroform

Sources & evidence

ORD record
ord-79b7a9f52d4b47abbab4f07df0d486f8
Source dataset
uspto-grants-2003_12
Patent number
US06656947B2

Reaction notes

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