Dimethyl Sulfate → Methyl 3-methoxy-1-phenyl-1H-indole-2-carboxylate

HRID 653144

Reaction equation

HRID 653144 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]([C:7]1[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]2[C:14]([C:15]=1[OH:16])=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6].S(OC)(O[CH3:27])(=O)=O>CN(C)C=O>[CH3:3][O:4][C:5]([C:7]1[N:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:9]2[C:14]([C:15]=1[O:16][CH3:27])=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6]

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 24758Sodium hydrideHCID 54687160Methyl 3-hydroxy-1-phenyl-1H-indole-2-carboxylate

Product 1

HCID 13344648Methyl 3-methoxy-1-phenyl-1H-indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 3.9 g (0.081 mole) of 50% sodium hydride/mineral oil in 85 ml of N,N-dimethylformamide under a nitrogen atmosphere was cooled in ice and treated portionwise over 90 minutes with 17.1 g (0.064 mole) of 3-hydroxy-1-phenyl-1H-indole-2-carboxylic acid methyl ester [P. Friedlander and K. Kunz, Chem. Ber., 55, 1597 (1922)]. The mixture was stirred in ice an additional one hour, 7.9 ml (10.5 g; 0.083 mole) of dimethyl sulfate was added dropwise over 15 minutes, the ice bath was removed, and stirring was continued for a total of 65 hours. The reaction mixture was added to 600 g of ice/water, acidified with 4.0N hydrochloric acid, and extracted with dichloromethane (4×250 ml). The combined organic layers were washed with water (3×500 ml), dried (anhydrous sodium sulfate), and evaporated to yield a crude residue of 3-methoxy-1-phenyl-1H-indole-2-carboxylic acid methyl ester, plus a small amount of N,N-dimethylformamide.

Workup

  1. temperaturewas cooled in ice
  2. customthe ice bath was removed
  3. stirringstirring
  4. customwas continued for a total of 65 hours
  5. additionThe reaction mixture was added to 600 g of ice/water
  6. extractionextracted with dichloromethane (4×250 ml)
  7. washThe combined organic layers were washed with water (3×500 ml)
  8. dry with materialdried (anhydrous sodium sulfate)
  9. customevaporated

Sources & evidence

ORD record
ord-194cd0e9b5cc4632925ad5586fe1be0a
Source dataset
uspto-grants-1987_06
Patent number
US04675332

Linked notes

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