Ethyl Acetate → HCID 21868721, compound

HRID 857464Notes

Reaction equation

HRID 857464 reaction equation
[C:1]([CH2:3][N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([I:13])[CH:11]=2)[CH:6]=[C:5]1[C:14](OCC)=O)#[N:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+].C(OCC)(=O)C>CCOCC>[I:13][C:10]1[CH:9]=[CH:8][C:7]2[CH:6]=[C:5]3[CH2:14][NH:2][CH2:1][CH2:3][N:4]3[C:12]=2[CH:11]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9855836Potassium sodium tartarateHCID 21226445Aluminium lithium hydrideHCID 21868730HCID 21868730, compound

Product 1

HCID 21868721HCID 21868721, compoundYield 31.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Ethyl 1-(cyanomethyl)-6-iodoindole-2-carboxylate (1.77 g, 5 mmol) was added portion-wise over 2 min to a stirred suspension of lithium aluminium hydride (0.48 g, 13 mmol) in ether (50 mL) at 0° C. under Ar. The reaction was then heated to reflux and stirred for 18 h. After allowing to cool to room temperature the mixture was poured into a mixture of saturated aqueous potassium sodium tartrate solution (150 mL) and ethyl acetate (100 mL). The mixture was filtered through celite and the biphasic filtrate was separated. The aqueous layer was extracted with ethyl acetate (2×50 mL) and the combined organic extracts were washed with brine (1×75 mL), dried (magnesium sulfate), filtered and the solvent removed under vacuum to leave a crude oil. The oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol, (9:1)] to give the product as a yellow solid (0.47 g, 32%, contains 15% of de-iodinated material). IR νmax (Nujol)/cm−1 3306, 2924, 2855, 1882, 1735, 1664, 1598, 1527, 1460, 1410, 1378, 1356, 1338, 1322, 1298, 1282, 1246, 1218, 1202, 1170, 1143, 1116, 1045, 1001, 984, 943, 919, 876, 840, 814, 773, 740, 698, 637, 617, 589, 522 and 488; NMR δH (400 MHz; CDCl3) 7.60 (1H, m), 7.35–7.37 (1H, m), 7.28 (1H, d, J 7.8 Hz), 6.15 (1H, m), 4.19 (2H, m), 3.94 (2H, t, J 5.8 Hz), 3.33 (2H, t, J 5.8 Hz), 1.79 (1H, br. s).

Workup

  1. temperatureThe reaction was then heated
  2. temperatureto reflux
  3. filtrationThe mixture was filtered through celite
  4. customthe biphasic filtrate was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
  6. washthe combined organic extracts were washed with brine (1×75 mL)
  7. dry with materialdried (magnesium sulfate)
  8. filtrationfiltered
  9. customthe solvent removed under vacuum
  10. customto leave a crude oil
  11. customThe oil was purified by flash column chromatography [SiO2; ethyl acetate-methanol, (9:1)]

Sources & evidence

ORD record
ord-352f39fffb9a499d8ae0a5281ad0d015
Source dataset
uspto-grants-2006_12
Patent number
US07145009B2

Reaction notes

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