Diisopropylamine → Ethyl 5-[1-(pyridin-3-yl)-1H-indol-3-yl]penta-2,4-dienoate

HRID 485334Notes

Reaction equation

HRID 485334 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][CH2:14][O:15][C:16](/[CH:18]=[CH:19]/[CH2:20]P(OCC)(OCC)=O)=[O:17].[N:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N:35]2[C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[C:37]([CH:44]=O)=[CH:36]2)[CH:30]=1>O1CCCC1.CCCCCC>[CH2:14]([O:15][C:16]([CH:18]=[CH:19][CH:20]=[CH:44][C:37]1[C:38]2[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=2)[N:35]([C:31]2[CH:30]=[N:29][CH:34]=[CH:33][CH:32]=2)[CH:36]=1)=[O:17])[CH3:13]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 5365783Triethyl 4-phosphonocrotonate, mixture of isomersHCID 13490349HCID 13490349, compoundHCID 178418339Butyllithium

Product 1

HCID 54103669Ethyl 5-[1-(pyridin-3-yl)-1H-indol-3-yl]penta-2,4-dienoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

A solution of 1.27 ml of diisopropylamine in 25 ml of tetrahydrofuran is cooled to -65° under nitrogen and 5.7 ml of 1.6M n-butyllithium in hexane is added. After 30 minutes at -65°, 2.0 ml of triethyl 4-phosphonocrotonate is added dropwise. The reaction mixture is stirred for 30 minutes before a solution of 2.0 g of N-(3-pyridyl)indole-3-carboxaldehyde in 20 ml of tetrahydrofuran is slowly added while maintaining the temperature less than -60°. When the addition is complete, cooling is suspended and the reaction mixture slowly warms to room temperature at which temperature it is stirred for 4 hours. The solvent is evaporated and the residue is partitioned between 30 ml of methylene chloride and 20 ml of half saturated ammonium chloride solution. The organic phase is washed with 20 ml of water, dried over sodium sulfate and evaporated to give an oil which crystallizes from hot ethyl acetate to yield 3-[4-(ethoxycarbonyl)butadienyl]-N-(3-pyridyl)-indole, m.p. 112°-113°.

Workup

  1. additionis slowly added
  2. temperaturewhile maintaining the temperature less than -60°
  3. additionWhen the addition
  4. temperaturecooling
  5. customslowly warms to room temperature at which temperature it
  6. customThe solvent is evaporated
  7. customthe residue is partitioned between 30 ml of methylene chloride and 20 ml of half saturated ammonium chloride solution
  8. washThe organic phase is washed with 20 ml of water
  9. dry with materialdried over sodium sulfate
  10. customevaporated
  11. customto give an oil which
  12. customcrystallizes from hot ethyl acetate

Sources & evidence

ORD record
ord-18411979e28c4fa1a9566c1f8071288c
Source dataset
uspto-grants-1985_08
Patent number
US04536505

Reaction notes

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