Dimethylformamide → Methyl 2-(3-chloro-4-cyanophenyl)acetate

HRID 1162511Notes

Reaction equation

HRID 1162511 reaction equation
[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[C:7]([Cl:19])[CH:6]=1.C([O-])(O)=O.[Na+].[CH3:26][N:27](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:20])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:26]#[N:27])=[C:7]([Cl:19])[CH:6]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 3564187Methyl 2-[3-chloro-4-(trifluoromethylsulfonyloxy)phenyl]acetate

Product 1

HCID 3564186Methyl 2-(3-chloro-4-cyanophenyl)acetate

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (3-chloro-4-trifluoromethanesulfonyloxy-phenyl)-acetic acid methyl ester 12 (24.5 g, 73.6 mmol) in dry DMF (45 mL) is combined with zinc cyanide (8.91 g, 75.9 mmol) and tetrakis(triphenylphosphine) palladium (8.50 g, 7.4 mmol). The mixture is stirred for 34 hours at 80° C., then cooled to room temperature, diluted with EtOAc (150 mL) and poured into a saturated NaHCO3 solution (150 mL). A white precipitate is removed by vacuum filtration. The organic layer of the filtrate is separated and washed with H2O. The organic layer is dried (MgSO4), filtered and concentrated. The remainder is purified by silica gel chromatography using 20% EtOAc/hexane to give (3-chloro-4-cyano-phenyl)acetic acid methyl ester 13 as a wax-like solid: 1H-NMR (400 MHz, CDCl3) δ=7.63 (d, J=8.0 Hz, 1H), 7.47 (d, J=1.2 Hz, 1H), 7.30 (dd, J=1.2 Hz, J=8.0 Hz, 1H), 3.72 (s, 3H), 3.69 (s, 2H). MS calculated for C10H9O2ClN (M+H+) 210.0, found 210.0.

Workup

  1. temperaturecooled to room temperature
  2. customA white precipitate is removed by vacuum filtration
  3. customThe organic layer of the filtrate is separated
  4. washwashed with H2O
  5. dry with materialThe organic layer is dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe remainder is purified by silica gel chromatography

Sources & evidence

ORD record
ord-1adb19982a6b4a238987ec5ea5226d8e
Source dataset
uspto-grants-2010_10
Patent number
US07820705B2

Reaction notes

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