Piperonal → Methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido(3,4-b)indole-3-carboxylate

HRID 1354552Notes

Reaction equation

HRID 1354552 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:17])[C@@H:5]([CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)[NH2:6].[CH:18]1[C:23]([CH:24]=O)=[CH:22][C:21]2[O:26][CH2:27][O:28][C:20]=2[CH:19]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C(=O)C.O>[CH3:2][O:3][C:4]([C@@H:5]1[NH:6][C@H:24]([C:23]2[CH:18]=[CH:19][C:20]3[O:28][CH2:27][O:26][C:21]=3[CH:22]=2)[C:9]2[NH:10][C:11]3[C:16]([C:8]=2[CH2:7]1)=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:17]

Participants

7

Reactant 4

HCID 8438PiperonalHCID 24436Sodium SulfateHCID 516892Sodium BicarbonateHCID 11448200methyl (2R)-2-amino-3-(1H-indol-3-yl)propanoate hydrochloride

Product 1

HCID 10269318Methyl (1R,3R)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido(3,4-b)indole-3-carboxylateYield 64.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of D-Tryptophan methyl ester hydrochloride (100 g) in N,N-Dimethyl acetamide (500 ml), added Piperonal (65 g) and sodium sulphate (56 g) and heated the reaction mass to 65–70° C. for 30–35 hours for completion of reaction. Reaction mass is then diluted with water, basified with sodium bicarbonate solution and extracted twice with dichloromethane (2×750 ml). The organic layer is then treated with aqueous hydrochloric acid (1000 ml). Dichloromethane is evaporated and the reaction mass is stirred for 6–10 hours at 55–60° C. Cooled the reaction mass to an ambient temperature and filtered the crude title compound in hydrochloride salt form. Then wet crude mass is charged in sodium bicarbonate solution and extracted twice with dichloromethane (2×750 ml). Dichloromethane layer is distilled out and the residual material is dissolved in Toluene and crystallized by addition of anti solvent like cyclohexane to get title compound (89.0 g).

Workup

  1. temperatureheated the reaction mass to 65–70° C. for 30–35 hours
  2. customfor completion of reaction
  3. customReaction mass
  4. extractionextracted twice with dichloromethane (2×750 ml)
  5. additionThe organic layer is then treated with aqueous hydrochloric acid (1000 ml)
  6. customDichloromethane is evaporated
  7. filtrationfiltered the crude title compound in hydrochloride salt form
  8. additionThen wet crude mass is charged in sodium bicarbonate solution
  9. extractionextracted twice with dichloromethane (2×750 ml)
  10. distillationDichloromethane layer is distilled out
  11. dissolutionthe residual material is dissolved in Toluene
  12. customcrystallized by addition of anti solvent like cyclohexane

Sources & evidence

ORD record
ord-57606e8dd60943448626144acb1d19dd
Source dataset
uspto-grants-2007_05
Patent number
US07223863B2

Reaction notes

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