Dimethylformamide → (2-Chloro-7-cyano-naphthalen-1-yl)-acetic acid ethyl ester

HRID 1968711Notes

Reaction equation

HRID 1968711 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13](OS(C(F)(F)F)(=O)=O)[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][CH:12]=[C:13]([C:26]#[N:27])[CH:14]=2)[CH:9]=[CH:8][C:7]=1[Cl:24])[CH3:2]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 86623472(2-Chloro-7-trifluoromethanesulfonyloxy-naphthalen-1-yl)-acetic acid ethyl ester

Product 1

HCID 66869743(2-Chloro-7-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-7-trifluoromethanesulfonyloxy-naphthalen-1-yl)-acetic acid ethyl ester (9.30 g, 23.43 mmol) is dissolved in DMF (80 ml) under an atmosphere of argon. Palladium(0) tetrakis(triphenylphosphane) (1.08 g, 0.9375 mmol) and zinc(II) cyanide (5.50 g, 46.87 mmol) are added. 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. After stirring for 15 minutes, filtration and concentration affords the crude reaction product. Purification by FCC (hexane/EtOAc 4:1) affords the title compound. 1H NMR (CDCl3, 400 MHz): δ 1.26 (t, J=8.8 Hz, 3H), 4.19 (q, J=8.8 Hz, 2H), 4.28 (s, 2H), 7.62-7.66 (m, 2H), 7.79 (d, J=9.9 Hz, 1H), 7.92 (d, J=9.9 Hz, 1H), 8.32 (s, 1H). ES+-MS: 274.2 [M+H]+.

Workup

  1. customconsumption of starting material
  2. temperatureThe suspension is cooled to RT
  3. additionpoured onto water
  4. filtrationfiltration and concentration
  5. customaffords the crude
  6. customreaction product
  7. customPurification by FCC (hexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-333d7a78e3c042cf9d6b4aecca740a65
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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