p-Toluenesulfonic acid monohydrate → Methyl 3-methyl-1H-indole-5-carboxylate

HRID 1851952Notes

Reaction equation

HRID 1851952 reaction equation
[CH:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[NH:5][CH:4]=1)=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.C(OCC)(=O)C>[CH3:1][C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[NH:5][CH:4]=1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 19606277Methyl 3-formyl-1H-indole-5-carboxylate

Product 1

HCID 23383527Methyl 3-methyl-1H-indole-5-carboxylateYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the methyl 3-formyl-1H-indole-5-carboxylate (893 mg, 4.4 mmol) in DMF (20 mL) was added the p-toluenesulfonic acid monohydrate (125 mg, 0.7 mmol) and the p-toluenesulfonyl hydrazide (982 mg, 5.3 mmol). The solution has been heated for 20 min at 100° C. The resulting mixture was diluted with ethyl acetate, washed with brine, dried over MgSO4 and concentrated. The crude product is dissolved in THF (40 mL) and NaBH3 CN (1.1 g, 17.6 mmol) was added. The solution has been heated for 8 h at 75° C. The resulting mixture was diluted with ethyl acetate, washed with a solution of 0.5 N HCl, a saturated solution of NaHCO3 and brine, dried over MgSO4 and concentrated. The crude product was purified by flash chromatography (Hexane/AcOEt, from 0 to 30%) to yield a white powder (500 mg, 2.6 mmol, 60%). ESI-MS (m/z): 190 [M+H]+.

Workup

  1. washwashed with brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. dissolutionThe crude product is dissolved in THF (40 mL)
  5. additionNaBH3 CN (1.1 g, 17.6 mmol) was added
  6. temperatureThe solution has been heated for 8 h at 75° C
  7. additionThe resulting mixture was diluted with ethyl acetate
  8. washwashed with a solution of 0.5 N HCl
  9. dry with materiala saturated solution of NaHCO3 and brine, dried over MgSO4
  10. concentrationconcentrated
  11. customThe crude product was purified by flash chromatography (Hexane/AcOEt, from 0 to 30%)

Sources & evidence

ORD record
ord-66976fd464df47ec9350b54f7f93e265
Source dataset
uspto-grants-2015_02
Patent number
US08957093B2

Reaction notes

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