1,1,3,3-Tetramethylguanidine → (Z)-2-Ethoxy-3-(1H-indol-5-yl)-acrylic Acid Ethyl Ester

HRID 2181182Notes

Reaction equation

HRID 2181182 reaction equation
[Cl-].[CH2:2]([O:4][CH:5]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:3].CN(C)C(=N)N(C)C.[CH:38]([C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][CH:44]=[CH:43]2)=O>ClCCl>[CH2:9]([O:8][C:6](=[O:7])/[C:5](/[O:4][CH2:2][CH3:3])=[CH:38]/[C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][CH:44]=[CH:43]2)[CH3:10]

Participants

5

Reactant 3

HCID 664601,1,3,3-Tetramethylguanidine2×HCID 589040Indole-5-carboxaldehydeHCID 11327835Phosphonium, (1,2-diethoxy-2-oxoethyl)triphenyl-, chloride (1:1)

Product 1

HCID 53309301(Z)-2-Ethoxy-3-(1H-indol-5-yl)-acrylic Acid Ethyl EsterYield 94.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 25.73 g of (1,2-diethoxy-2-oxoethyl)triphenyl phosphonium chloride in 200 ml of dichloromethane was added at 0° C. 8.0 ml of tetramethyl guanidine and the mixture was warmed to 22° C. The mixture was treated with 5.81 g of 5-formyl-indole and stirring was continued at 40° C. for 16 h. The mixture was treated again with 25.73 g of the Wittig salt and 8.0 ml of tetramethyl guanidine and stirring was continued at 40° C. for 24 h after which time the conversion was complete. The mixture was evaporated and the residue partitioned between AcOEt and water. The organic layer was dried, evaporated and the residue chromatographed on silica (n-hexane/AcOEt, 2:1) to give 9.80 g of the title compound as an oil which solidified on storing at 22° C. to give a pale yellow solid. MS: (M)+ 259.2.

Workup

  1. stirringstirring
  2. waitwas continued at 40° C. for 24 h
  3. customThe mixture was evaporated
  4. customthe residue partitioned between AcOEt and water
  5. customThe organic layer was dried
  6. customevaporated
  7. customthe residue chromatographed on silica (n-hexane/AcOEt, 2:1)

Sources & evidence

ORD record
ord-fa557c8a5d664180ae77c10be72b8998
Source dataset
uspto-grants-2005_05
Patent number
US06890947B2

Reaction notes

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