Acetonitrile → (E)-N,N-Diethyl-3-{4-[6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophene-3-carbonyl]phenyl}acrylamide

HRID 400200Notes

Reaction equation

HRID 400200 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[C:11]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:12]=3[S:13][C:14]=2[C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=[O:9])=[CH:4][CH:3]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[CH2:49]([N:51]([CH2:56][CH3:57])[C:52](=[O:55])[CH:53]=[CH2:54])[CH3:50].C(#N)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[CH2:49]([N:51]([CH2:56][CH3:57])[C:52](=[O:55])/[CH:53]=[CH:54]/[C:2]1[CH:3]=[CH:4][C:5]([C:8]([C:10]2[C:11]3[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][C:12]=3[S:13][C:14]=2[C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=[O:9])=[CH:6][CH:7]=1)[CH3:50]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 17583N,N-DiethylacrylamideHCID 80271Tri-o-tolylphosphineHCID 189443264-Bromophenyl-[6-Hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl]methanone

Product 1

HCID 18944327(E)-N,N-Diethyl-3-{4-[6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thiophene-3-carbonyl]phenyl}acrylamideYield 55.1%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
85 °C

Procedure

To a screw cap seal tube is added 0.83 g (2.0 mmol) of the product from Example 2, 0.25 g (0.82 mmol) of tri-o-tolylphosphine, 0.30 g (2.3 mmol) of N,N-diethyl acrylamide, 0.045 g (0.21 mmol) of palladium acetate, 40 mL of acetonitrile and 4 mL of triethylamine. The solution was purged with nitrogen then capped and heated to 85° C. for 15 hours. At the end of this time, the solution was concentrated, then taken up in 100 mL of water:ethyl acetate (1:2). The organic layer was separated and the water layer extracted once with ethyl acetate. The ethyl acetate layers were combined, dried (MgSO4) and concentrated. The residue subjected to column chromatography on silica. Elution first with 60% ethyl acetate:hexane followed by ethyl acetate:hexane:isopropanol (60:35:5) yielded 0.52 g of product (55%) which was crystallized from chloroform:acetone:hexane mp 159°-163° C. (soft).

Workup

  1. customTo a screw cap
  2. customseal tube
  3. customThe solution was purged with nitrogen
  4. customthen capped
  5. concentrationAt the end of this time, the solution was concentrated
  6. customThe organic layer was separated
  7. extractionthe water layer extracted once with ethyl acetate
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. washElution first with 60% ethyl acetate

Sources & evidence

ORD record
ord-165741de52604984991db31e15b884bc
Source dataset
uspto-grants-1998_10
Patent number
US05827876

Reaction notes

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