Dimethylformamide → 1H-Indole-3-carboxylic acid, 1,1-dimethylethyl ester

HRID 1821940Notes

Reaction equation

HRID 1821940 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([OH:12])=[O:11])=[CH:2]1.CN(C=O)C.S(Cl)(Cl)=O.[C:22](O)([CH3:25])([CH3:24])[CH3:23]>C1COCC1.O>[C:22]([O:11][C:10]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1)=[O:12])([CH3:25])([CH3:24])[CH3:23]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 6386tert-ButanolHCID 24386Thionyl ChlorideHCID 69867Indole-3-Carboxylic Acid

Product 1

HCID 123081731H-Indole-3-carboxylic acid, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1.00 g (6.21 mmol) indole-3-carboxylic acid is dissolved in 150 ml absolute THF, mixed with 0.05 g (0.68 mmol) absolute DMF as well as with 1.48 g (12.5 mmol) thionylchloride and stirred at room temperature for 1 hour. Following the drop-wise addition of 2.51 g (24.8 mmol) tiethylamine and of 9.20 g (124 mmol) tert-butanol and heating under reflux for 2 hours, hydrolysis of the cooled reaction mixture is carried out in water. Three extractions with diethyl ether, concentration to half the volume on the rotary evaporator, washing with 5% sodium carbonate solution and with saturated NaCl solution, drying on sodium sulfate, filtration and reconcentration on the rotary evaporator leave as a crude product a brown oil which is purified on silica gel by means of column chromatography (flow agent: petroleum ether/ethyl acetate 90:10) and yields the product as a yellow oil.

Workup

  1. additionthe drop-wise addition of 2.51 g (24.8 mmol) tiethylamine
  2. temperatureunder reflux for 2 hours
  3. customhydrolysis of the cooled reaction mixture
  4. extractionThree extractions
  5. concentrationwith diethyl ether, concentration to half the volume
  6. customon the rotary evaporator
  7. washwashing with 5% sodium carbonate solution and with saturated NaCl solution
  8. customdrying on sodium sulfate, filtration and reconcentration on the rotary evaporator
  9. customleave as a crude product a brown oil which
  10. customis purified on silica gel by means of column chromatography (flow agent: petroleum ether/ethyl acetate 90:10)

Sources & evidence

ORD record
ord-a89170fd7bf2434eaa362f3f426f8efe
Source dataset
uspto-grants-2009_10
Patent number
US07608633B2

Reaction notes

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