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

HRID 431790Notes

Reaction equation

HRID 431790 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-0ed67bcc42204715a66b148a9aed9850
Source dataset
uspto-grants-2003_12
Patent number
US06660756B2

Reaction notes

Loading…