Dimethyl Sulfoxide → (Z)-ethyl 4-(2-iodo-4,5-dimethoxybenzamido)but-2-enoate

HRID 2175714Notes

Reaction equation

HRID 2175714 reaction equation
CS(C)=[O:3].[C:5](Cl)(=[O:9])[C:6](Cl)=O.O[CH2:12][CH2:13][NH:14][C:15](=[O:27])[C:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[CH:18][C:17]=1[I:26].CCN([CH2:33][CH3:34])CC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C(Cl)Cl>[I:26][C:17]1[CH:18]=[C:19]([O:24][CH3:25])[C:20]([O:22][CH3:23])=[CH:21][C:16]=1[C:15]([NH:14][CH2:13]/[CH:12]=[CH:34]\[C:33]([O:9][CH2:5][CH3:6])=[O:3])=[O:27]

Participants

7

Reactant 5

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 65578Oxalyl chlorideHCID 67087759N-(2-hydroxyethyl)-2-iodo-4,5-dimethoxybenzamide

Product 1

HCID 70935552(Z)-ethyl 4-(2-iodo-4,5-dimethoxybenzamido)but-2-enoateYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of dry DMSO (0.453 mL, 6.4 mmol) in DCM (2 mL) was added dropwise to a solution of oxalyl chloride (0.338 mL, 4 mmol) in DCM (5 mL) at −78° C. The reaction was stirred for 30 min at −78° C. then a solution of N-(2-hydroxyethyl)-2-iodo-4,5-dimethoxybenzamide (702 mg, 2 mmol) in DCM (3 mL) was added via cannula. The mixture was stirred at −78° C. for 1 hour then dry Et3N (1.7 mL, 12 mmol) was added slowly. Stirring was continued at −78° C. for 1 hour by which time the formation of the aldehyde was complete (monitored by TLC). Solid Ph3P═CHCOOEt (1.0 g, 3 mmol) was then added and the reaction was allowed to warm slowly to room temperature overnight. The solvent was removed under reduced pressure and the crude product was purified by flash column using petroleum ether/ethyl acetate (from 6:1 to 3:1) as eluent to give (Z)-ethyl 4-(2-iodo-4,5-dimethoxybenzamido)but-2-enoate (280 mg, 34%). LC-MS (ES-API); rt 8.46 min; m/z calculated for C15H18INO5 [M+H]+ 420.0, found 420.0.

Workup

  1. stirringThe mixture was stirred at −78° C. for 1 hour
  2. stirringStirring
  3. waitwas continued at −78° C. for 1 hour by which time
  4. temperatureto warm slowly to room temperature overnight
  5. customThe solvent was removed under reduced pressure
  6. customthe crude product was purified by flash column

Sources & evidence

ORD record
ord-8b115c159e084d088222a97a04ae4bf7
Source dataset
uspto-grants-2015_06
Patent number
US09062076B2

Reaction notes

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