Acetic Acid → Methyl-(2E)-2-cyano-3-(2,3-dihydro-1-benzofuran-5-yl)-2-butenoate

HRID 22930

Reaction equation

HRID 22930 reaction equation
[C:1]([C:4]1[CH:12]=[CH:11][C:7]2[O:8][CH2:9][CH2:10][C:6]=2[CH:5]=1)(=O)[CH3:2].[C:13]([CH2:15][C:16]([O:18][CH3:19])=[O:17])#[N:14].C(N)C1C=CC=CC=1.C(O)(=O)C>C1(C)C=CC=CC=1>[CH3:19][O:18][C:16](=[O:17])/[C:15](/[C:13]#[N:14])=[C:1](/[C:4]1[CH:12]=[CH:11][C:7]2[O:8][CH2:9][CH2:10][C:6]=2[CH:5]=1)\[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7504BenzylamineHCID 7747Methyl cyanoacetateHCID 1452201-(2,3-Dihydro-5-benzofuranyl)ethanone

Product 1

HCID 69746774Methyl-(2E)-2-cyano-3-(2,3-dihydro-1-benzofuran-5-yl)-2-butenoateYield 60.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 5-acetyl-2,3-dihydrobenzo[b]furan (Aldrich) (1 g, 6.17 mmol) in toluene (60 ml) was added methyl cyanoacetate (0.60 ml, 6.78 mmol), benzylamine (0.07 ml, 0.61 mmol) and acetic acid (0.3 ml, 5.3 mmol) and the whole refluxed in a Dean-Stark apparatus for 16 h. The reaction mixture was cooled, washed with 2N HCl (30 ml), NaHCO3 (30 ml), brine (30 ml), dried (MgSO4) and evaporated to a yellow residue. This residue was purified by column chromatography using 15-20% EtOAc in pentane as eluant to provide the title product (902 mg, 60%); 1HNMR (400 MHz, CDCl3) δ: 2.65 (s, 3H), 3.25 (t, 2H), 3.9 (s, 3H), 4.6 (t, 2H), 6.8 (d, 1H), 7.25 (d, 1H), 7.8 (s, 1H); LRMS: M+NH4+, 261. (ES+).

Workup

  1. temperaturethe whole refluxed in a Dean-Stark apparatus for 16 h
  2. temperatureThe reaction mixture was cooled
  3. washwashed with 2N HCl (30 ml), NaHCO3 (30 ml), brine (30 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated to a yellow residue
  6. customThis residue was purified by column chromatography

Sources & evidence

ORD record
ord-8e35362516b442d983fbea020c66b3ad
Source dataset
uspto-grants-2005_02
Patent number
US06849649B2

Linked notes

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