Water → Ethyl 3-chloro-8-cyanonaphthalene-2-carboxylate

HRID 1968757Notes

Reaction equation

HRID 1968757 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15]([Cl:16])=[CH:14][C:13]2[C:8](=[C:9](OS(C(F)(F)F)(=O)=O)[CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=[O:5])[CH3:2].O.[CH3:26][N:27](C)C=O>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:15]([Cl:16])=[CH:14][C:13]2[C:8](=[C:9]([C:26]#[N:27])[CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 6228DimethylformamideHCID 866257923-Chloro-8-trifluoromethanesulfonyloxy-naphthalene-2-carboxylic acid ethyl ester

Product 1

HCID 66880747Ethyl 3-chloro-8-cyanonaphthalene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
125 °C

Procedure

Zn(CN)2 (1.50 g, 12.80 mmol, 2.0 equiv) and Pd(PPh3)4 (296 mg, 0.26 mmol, 0.04 equiv) were added at room temperature under an atmosphere of argon to a degassed solution of 3-chloro-8-trifluoromethanesulfonyloxy-naphthalene-2-carboxylic acid ethyl ester (2.45 g, 6.40 mmol) in N,N-dimethylformamide (25 ml). The mixture was heated to 125° C. After 30 minutes, TLC analysis indicated complete conversion. After cooling, water was added, and the mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (gradient of hexane/EtOAc 100:0 to 90:10) afforded the title compound (1.43 g, 86%, 1:1.3 mixture of regioisomers A:B) as a white solid. For analytical purposes, the regioisomers could be separated by careful chromatography on silica gel. Regioisomer A: 1H NMR (400 MHz, CDCl3): δ=8.41 (s, 1H), 8.32 (s, 1H), 8.13 (br d, J=8.3 Hz, 1H), 8.01 (dd, J=7.1/1.0 Hz, 1H), 7.60 (dd, J=8.3/7.3 Hz, 1H), 4.47 (q, J=7.1 Hz, 2H), 1.45 (t, J=7.1 Hz, 3H). MS (ES+): 260 (M+H)+. Regioisomer B: 1H NMR (400 MHz, CDCl3): δ=8.65 (s, 1H), 8.02 (d, J=8.3 Hz, 1H), 8.02 (s, 1H), 7.96 (dd, J=7.4/1.3 Hz, 1H), 7.65 (dd, J=8.3/7.4 Hz, 1H), 4.49 (q, J=7.1 Hz, 2H), 1.46 (t, J=7.3 Hz, 3H). MS (ES+): 260 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. extractionthe mixture was extracted with EtOAc
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification via flash chromatography (gradient of hexane/EtOAc 100:0 to 90:10)

Sources & evidence

ORD record
ord-aee98247e93346149b15bae0d70603ee
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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