Chloroform hexane → Ethyl 2-amino-4-chloro-1H-indole-3-carboxylate

HRID 1878508Notes

Reaction equation

HRID 1878508 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH:5]([CH:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]1(Cl)[N+:14]([O-])=O)[C:6]#[N:7])[CH3:2].CCCCCC.C(Cl)(Cl)[Cl:26]>C(O)(=O)C.[Zn]>[CH2:1]([O:3][C:4]([C:5]1[C:8]2[C:9](=[CH:10][CH:11]=[CH:12][C:13]=2[Cl:26])[NH:14][C:6]=1[NH2:7])=[O:18])[CH3:2]

Participants

5

Reactant 2

HCID 21585165Chloroform hexaneHCID 131728954Ethyl(2-chloro-2-nitrophenyl)(cyano)acetate

Product 1

HCID 45103996Ethyl 2-amino-4-chloro-1H-indole-3-carboxylate

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 176Acetic AcidSolvent

Conditions

Temperature
55 °C

Procedure

4 (18 g, 67 mmol), in 250 mL glacial acetic acid, was treated with a single charge of 18 g of zinc dust. The mixture was heated at 55° C. for 45 minutes. Later, 6 g more zinc dust was added. After heating for another 105 minutes, the yellow mixture was filtered through a pad of celite. The pad was washed with acetic acid and the filtrate was concentrated to a residue that was distributed between chloroform and water. The organic phase was washed with NaHCO3 (5%) to provide a pink precipitate which was filtered, dried over P2O5, dissolved in methanol, added silica gel and converted to a silica gel plug by removing the solvent under reduced pressure. The plug was transferred on top of a column packed with silica gel, ten times the weight of plug, eluted with hexane, chloroform, 5% ethylacetate in chloroform and 10% ethylacetate in chloroform. Fractions containing the product 5 (TLC) were pooled and evaporated to give a pink solid. The overall yield from 3 to 5 was 63%. TLC Rf 0.187 (hexane-chloroform 1:1); mp 140-142° C.; 1H NMR (DMSO-d6) δ 1.25-1.28 (t, 3H, CH3); 4.18-4.20 (q, 2H, CH2); 6.85 (bs, 2H, 2-NH2, exch); 6.92-7.09 (m, 3H, phenyl); 10.93 (bs, 1H, 9-NH, exch). Anal. Calculated (C11H11ClN2O2): C, 55.36; H, 4.65; N, 11.74; Cl, 14.85. Found: C, 55.39; H, 4.60; N, 11.65; Cl, 14.96.

Workup

  1. temperatureAfter heating for another 105 minutes
  2. filtrationthe yellow mixture was filtered through a pad of celite
  3. washThe pad was washed with acetic acid
  4. concentrationthe filtrate was concentrated to a residue that
  5. washThe organic phase was washed with NaHCO3 (5%)
  6. customto provide a pink precipitate which
  7. filtrationwas filtered
  8. dry with materialdried over P2O5
  9. dissolutiondissolved in methanol
  10. additionadded silica gel
  11. customby removing the solvent under reduced pressure
  12. washeluted with hexane, chloroform, 5% ethylacetate in chloroform and 10% ethylacetate in chloroform
  13. additionFractions containing the product 5 (TLC)
  14. customevaporated
  15. customto give a pink solid
  16. customThe overall yield from 3 to 5

Sources & evidence

ORD record
ord-6d2a405ab9e040289f9e869644b2a371
Source dataset
uspto-grants-2012_11
Patent number
US08314114B2

Reaction notes

Loading…