Ethanol → HCID 10638353, compound

HRID 366821Notes

Reaction equation

HRID 366821 reaction equation
[K].CCO.[C:5]([O:12][CH2:13][CH3:14])(=[O:11])[C:6](OCC)=O.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH3:32])[C:20]([N+:29]([O-])=O)=[C:21]([O:23][CH2:24][CH2:25][N:26]([CH3:28])[CH3:27])[CH:22]=1>CCOCC>[CH3:28][N:26]([CH3:27])[CH2:25][CH2:24][O:23][C:21]1[CH:22]=[C:17]([O:16][CH3:15])[CH:18]=[C:19]2[C:20]=1[NH:29][C:6]([C:5]([O:12][CH2:13][CH3:14])=[O:11])=[CH:32]2

Participants

6

Reactant 4

HCID 702EthanolHCID 7268Diethyl OxalateHCID 5462222Potassium2×HCID 10610946HCID 10610946, compound

Product 1

HCID 10638353HCID 10638353, compoundYield 18.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of potassium (0.308 g, 7.87 mmol) in xylenes (6 mL) was heated to 100° C. and stirred rapidly as it was allowed to cool. The xylenes were removed and the potassium was washed with Et2O (×3) and covered with Et2O (10 mL). The mixture was treated with absolute EtOH (1.30 mL, 22.2 mmol) and stirred at reflux until the potassium had dissolved (3 h). The cooled mixture was treated with diethyl oxalate (1.07 mL, 7.87 mmol) then with a solution of the above nitrotoluene (2.00 g, 7.87 mmol) in dry Et2O (5 mL). After 115 h, the dark red precipitate was removed by filtration and washed with Et2O. The red solid (1.189 g) was dissolved in absolute EtOH (45 mL), acidified with AcOH (0.78 mL), and hydrogenated over Pd/C (10%, 0.44 g) at 1 atm H2 for 8 h. The mixture was filtered through Celite, concentrated, diluted with 0.2 M aqueous Na2CO3 (100 mL), and extracted with EtOAc (×4). The combined extracts were washed with water (×2), dried (Na2SO4), evaporated and purified by flash chromatography (2% Et3N/EtOAc) to give ethyl 7-[2-(dimethylamino)-ethoxy]-5-methoxyindole-2-carboxylate as a clear oil (0.44 g, 18%). 1H NMR (CDCl3) δ 10.93 (br s, 1 H, NH), 7.09 (d, J=2.1 Hz, 1 H, H-3), 6.67 (d, J=2.0 Hz, 1 H, H-4), 6.43 (d, J=2.0 Hz, 1 H, H-6), 4.38 (q, J=7.0 Hz, 2 H, OCH2CH3), 4.16 (t, J=6.5 Hz, 2 H, OCH2CH2N), 3.88 (s, 3 H, OCH3), 2.79 (t, J=7.0 Hz, 2 H, NCH2), 2.37 (s, 6 H, N(CH3)2), 1.40 (t, J=6.5 Hz, 3 H, OCH2CH3); 13C NMR δ 161.9 (CO2), 155.0, 146.0, 128.1, 127.7, 124.9 (C-2, 3a, 5, 7, 7a), 108.1 (C-3), 99.1 (C-4), 94.6 (C-6), 65.9 (OCH2CH2N), 60.6 (OCH2CH3), 58.3 (NCH2), 55.6 (OCH3), 45.1 (N(CH3)2), 14.4 (OCH2CH3). Calc for C16H22N2O4, M+306.1580. Found, 306.1577. Starting material (0.77 g, 39%) was recovered from the ethereal washes by extraction into acid, basification, and extraction with Et2O.

Workup

  1. temperatureto cool
  2. customThe xylenes were removed
  3. washthe potassium was washed with Et2O (×3)
  4. stirringstirred
  5. dissolutionhad dissolved (3 h)
  6. customthe dark red precipitate was removed by filtration
  7. washwashed with Et2O
  8. dissolutionThe red solid (1.189 g) was dissolved in absolute EtOH (45 mL)
  9. waithydrogenated over Pd/C (10%, 0.44 g) at 1 atm H2 for 8 h
  10. filtrationThe mixture was filtered through Celite
  11. concentrationconcentrated
  12. additiondiluted with 0.2 M aqueous Na2CO3 (100 mL)
  13. extractionextracted with EtOAc (×4)
  14. washThe combined extracts were washed with water (×2)
  15. dry with materialdried (Na2SO4)
  16. customevaporated
  17. custompurified by flash chromatography (2% Et3N/EtOAc)

Sources & evidence

ORD record
ord-610723a63626473a8103c50d398ecd83
Source dataset
uspto-grants-2000_10
Patent number
US06130237

Reaction notes

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