Ethyl iodoacetate → Ethyl 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-yl-2,3-dihydrothiophene-2-carboxylate

HRID 572605Notes

Reaction equation

HRID 572605 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[C:10]([C:13]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[S:14])[C:11]#[N:12])=[CH:5][CH:4]=1.I[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24].CCN(C(C)C)C(C)C>C(#N)C>[C:11]([C:10]1[CH:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[S:14][C:13]=1[N:15]1[CH2:16][CH2:17][O:18][CH2:19][CH2:20]1)#[N:12]

Participants

5

Reactant 3

HCID 12183Ethyl iodoacetateHCID 81531DiisopropylethylamineHCID 866375463-(4-Methoxyphenyl)-2-(morpholin-4-ylcarbonothioyl)acrylonitrile

Product 1

HCID 68628637Ethyl 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-yl-2,3-dihydrothiophene-2-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-(4-methoxyphenyl)-2-(morpholin-4-ylcarbonothioyl)acrylonitrile (from step 1), ethyl iodoacetate (0.25 mL, 2.1 mmol) and DIPEA (0.5 mL, 2.9 mmol) was dissolved in ACN (2 mL) and subjected to MWI at 150° C. for 10 min. The mixture was allowed to cool and was concentrated. The residue was diluted with 5% sodium bisulfite solution and extracted with EtOAc. The organic solutions were combined, washed with sat NaHCO3 and brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give ethyl 4-cyano-3-(4-methoxyphenyl)-5-morpholin-4-yl-2,3-dihydrothiophene-2-carboxylate (0.168 g, 63% over two steps). LCMS: (AA) ES+ 375, ES− 373.

Workup

  1. temperatureto cool
  2. concentrationwas concentrated
  3. additionThe residue was diluted with 5% sodium bisulfite solution
  4. extractionextracted with EtOAc
  5. washwashed with sat NaHCO3 and brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-49b4ce3181c742e383dc52f1851a3ccf
Source dataset
uspto-grants-2015_05
Patent number
US09029411B2

Reaction notes

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