Water → Diethyl 1H-indole-2,6-dicarboxylate

HRID 1748242Notes

Reaction equation

HRID 1748242 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[C:5](=O)[CH2:6][C:7]1[CH:17]=[CH:16][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][C:8]=1[N+:18]([O-])=O)[CH3:2].O.CCOC(C)=O>C(O)(=O)C.[Zn]>[NH:18]1[C:8]2[C:7](=[CH:17][CH:16]=[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:9]=2)[CH:6]=[C:5]1[C:4]([O:3][CH2:1][CH3:2])=[O:22]

Participants

6

Reactant 3

HCID 962WaterHCID 8857Ethyl AcetateHCID 58767563Ethyl 4-(3-ethoxy-2,3-dioxopropyl)-3-nitrobenzoate

Product 1

HCID 44754779Diethyl 1H-indole-2,6-dicarboxylateYield 58.9%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
75 °C

Procedure

Ethyl 4-(3-ethoxy-2,3-dioxopropyl)-3-nitrobenzoate (91 g, 0.29 mol) is suspended in 800 mL of acetic acid and it is heated with stirring to 75° C. Once the solid is dissolved, water (600 mL) is added. Zinc dust (189 g, 2.9 mol) is added carefully in small portions and the reaction temperature is kept below 85° C. The mixture is then stirred vigorously for 1 hour after the addition. EtOAc (1500 mL) is added and the mixture was filtered through Celite. The solid is washed with more EtOAc (1500 mL) and the filtrates are combined, washed twice with water (1500 mL), four times with saturated NaHCO3 (1000 mL), and once with brine (1000 mL). The filtrate is dried (Na2SO4), filtered, and concentrated to afford the crude compound which was recrystallized from toluene to afford the title compound (44.6 g, 58%) as a yellow powder.

Workup

  1. temperatureit is heated
  2. dissolutionOnce the solid is dissolved
  3. customis kept below 85° C
  4. stirringThe mixture is then stirred vigorously for 1 hour
  5. additionafter the addition
  6. filtrationthe mixture was filtered through Celite
  7. washThe solid is washed with more EtOAc (1500 mL)
  8. washwashed twice with water (1500 mL), four times with saturated NaHCO3 (1000 mL)
  9. dry with materialThe filtrate is dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford the crude compound which
  13. customwas recrystallized from toluene

Sources & evidence

ORD record
ord-dd2fd7a2a70443f6ba3298a9a22a5d97
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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