Tetrahydrofuran → [3-(2-Ethoxycarbonyl)indolyl]acetaldehyde

HRID 982031Notes

Reaction equation

HRID 982031 reaction equation
[Cl-].[CH3:2][O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C([Li])CCC.[CH:29]([C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][C:32]=1[C:40](OCC)=O)=[O:30].[O:45]1[CH2:49][CH2:48]CC1>C(OCC)(=O)C>[CH3:48][CH2:49][O:45][C:29]([C:31]1[C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[NH:33][C:32]=1[CH2:40][CH:2]=[O:3])=[O:30]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 5107764ethyl 3-formyl-1H-indole-2-carboxylateHCID 178418339Butyllithium

Product 1

HCID 88135268[3-(2-Ethoxycarbonyl)indolyl]acetaldehydeYield 48%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 11.95 g (34.9 mmol) of methoxymethyltriphenylphosphonium chloride in 200 ml of anhydrous tetrahydrofuran was cooled to 0° C. under N2 atmosphere and treated dropwise with 14.3 ml (35.8 mmol) of n-butyllithium. The resulting solution was stirred for 15 min, treated with 3.70 g (17 mmol) of the resultant compound of Example 97, and stirred at ambient temperature for 3 h. After concentration of the solvent in vacuo, and the residue was taken up in ethyl acetate, washed sequentially with water and saturated brine, dried over MgSO4, and concentrated. The crude mixture of vinyl ethers was partially purified by silica gel chromatography using 6:1 hexane:ethyl acetate. The mixture (2.98 g, 71%) was subsequently treated with 20 ml of 1M HCl and 40 ml of tetrahydrofuran and heated at reflux for 6 h. After cooling, the solution was partitioned between ether and saturated aqueous NaHCO3, dried over MgSO4, and concentrated. Purification by silica gel chromatography using 4:1 hexane:ethyl acetate gave 1.35 g (48%) of the desired compound which was recrystallized from ethyl acetate/hexane. 1H NMR (CDCl3) δ 1.42 (t,J=7 Hz,3H), 4.17 (d,J=2 Hz,2H), 4.42 (q,J=7 Hz,2H), 7.19 (ddd,J=8,7,1 Hz,1H), 7.37 (ddd,J=8,7,1 Hz), 7.43 (br d,J=8 Hz,1H), 7.61 (br d,J=8 Hz,1H), 8.94 (br s,1H), 9.73 (t,J=2 Hz,1H). Mass spectrum: (M+H)+ =232.

Workup

  1. stirringstirred at ambient temperature for 3 h
  2. washwashed sequentially with water and saturated brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. additionThe crude mixture of vinyl ethers
  6. customwas partially purified by silica gel chromatography
  7. additionThe mixture (2.98 g, 71%) was subsequently treated with 20 ml of 1M HCl and 40 ml of tetrahydrofuran
  8. temperatureheated
  9. temperatureat reflux for 6 h
  10. temperatureAfter cooling
  11. customthe solution was partitioned between ether and saturated aqueous NaHCO3
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated
  14. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-6494ac1a247b419398ac7c882e4d2db1
Source dataset
uspto-grants-1991_02
Patent number
US04994477

Reaction notes

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