Sodium Cyanide → (5-Cyano-2-methyl-benzofuran-3-yl)-acetic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:10]2[CH:11]=[C:12](Br)[CH:13]=[CH:14][C:9]=2[O:8][C:7]=1[CH3:16])[CH3:2].[C:18]([Cu])#[N:19].[C-]#N.[Na+]>CN(C=O)C.O>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:10]2[CH:11]=[C:12]([C:18]#[N:19])[CH:13]=[CH:14][C:9]=2[O:8][C:7]=1[CH3:16])[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 165 °C
Procedure
A mixture of (5-bromo-2-methyl-benzofuran-3-yl)-acetic acid ethyl ester (6.8 g, 22.9 mmol) and CuCN (3.1 g, 34.3 mmol) in anhydrous DMF (20 mL) is heated for 16 h at reflux (165° C.) under an argon atmosphere. After cooling to room temperature a solution of NaCN (5.8 g, 114 mmol) in water (30 mL) is added. The reaction mixture is partitioned between water and toluene, the layers are separated and the aqueous phase is extracted with toluene. The combined organic layers are washed with a 10% aqueous NaCN solution and brine, dried over Na2SO4, filtered and concentrated at reduced pressure to afford the title compound as a brown solid (4.31 g, 17.7 mmol, 77%). 1H NMR (400 MHz, CDCl3, 298 K): δ=7.82 (d, J=1.7 Hz, 1H), 7.51-7.43 (m, 2H), 4.16 (q, J=7.1 Hz, 2H), 3.59 (s, 2H), 2.46 (s, 3H), 1.26 (t, J=7.1 Hz, 3H). MS (ES+): 244 (M(C14H13NO3)+H)+.
Workup
- temperatureis heated for 16 h
- additionis added
- customThe reaction mixture is partitioned between water and toluene
- customthe layers are separated
- extractionthe aqueous phase is extracted with toluene
- washThe combined organic layers are washed with a 10% aqueous NaCN solution and brine
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated at reduced pressure
Sources & evidence
- ORD record
- ord-4649e27bf508478d9741bafe0496881d
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08742132B2
Reaction notes
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