Dimethylformamide → (2-Chloro-6-cyano-naphthalen-1-yl)-acetic acid ethyl ester

HRID 639200Notes

Reaction equation

HRID 639200 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][C:12](OS(C(F)(F)F)(=O)=O)=[CH:13][CH:14]=2)[CH:9]=[CH:8][C:7]=1[Cl:24])[CH3:2].[CH3:26][N:27](C=O)C>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.[Pd].[C-]#N.[Zn+2].[C-]#N>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([C:26]#[N:27])=[CH:13][CH:14]=2)[CH:9]=[CH:8][C:7]=1[Cl:24])[CH3:2]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86623398(2-Chloro-6-trifluoromethanesulfonyloxy-naphthalen-1-yl)-acetic acid ethyl ester

Product 1

HCID 68704275(2-Chloro-6-cyano-naphthalen-1-yl)-acetic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
125 °C

Procedure

(2-Chloro-6-trifluoromethanesulfonyloxy-naphthalen-1-yl)-acetic acid ethyl ester (3.59 g, 9.04 mmol) is dissolved in DMF (30 ml) under an atmosphere of argon. After addition of palladium(0) tetrakis(triphenylphosphane) (418 mg, 0.36 mmol) and zinc(II) cyanide (2.12 g, 18.09 mmol), the reaction mixture is heated to 125° C. After 1 h, TLC analysis indicates complete consumption of starting material. The suspension is cooled to RT and poured onto water. Extraction with EtOAc is followed by washing the organic layer with 1 M aqueous HCl, sat. aqueous NaHCO3 solution and brine. After drying over Na2SO4 and removal of solvent, purification by FCC (hexane/EtOAc 3:1) affords the title compound. 1H NMR (d6-DMSO, 400 MHz): δ 1.06 (t, J=8 Hz, 3H), 3.98 (q, J=8 Hz, 2H), 4.24 (s, 2H), 7.66 (d, J=10 Hz, 1H), 7.79 (d, J=10 Hz, 1H), 7.96 (d, J=10 Hz, 1H), 8.13 (d, J=10 Hz, 1H), 8.54 (s, 1H).

Workup

  1. customconsumption of starting material
  2. temperatureThe suspension is cooled to RT
  3. additionpoured onto water
  4. extractionExtraction with EtOAc
  5. washby washing the organic layer with 1 M aqueous HCl, sat. aqueous NaHCO3 solution and brine
  6. dry with materialAfter drying over Na2SO4 and removal of solvent, purification by FCC (hexane/EtOAc 3:1)

Sources & evidence

ORD record
ord-d0ee6f39e8a54df08c987918d63e38b7
Source dataset
uspto-grants-2010_04
Patent number
US07691861B2

Reaction notes

Loading…