Acetic Acid → Ethyl 3-chloro-8-formylnaphthalene-2-carboxylate

HRID 505244Notes

Reaction equation

HRID 505244 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:15]([Cl:16])=[CH:14][C:13]2[C:8](=[C:9]([C:17]#N)[CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=[O:5])[CH3:2].CC(O)=[O:21].O>[Ni].N1C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:15]([Cl:16])=[CH:14][C:13]2[C:8](=[C:9]([CH:17]=[O:21])[CH:10]=[CH:11][CH:12]=2)[CH:7]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 66880747Ethyl 3-chloro-8-cyanonaphthalene-2-carboxylate

Product 1

HCID 71424625Ethyl 3-chloro-8-formylnaphthalene-2-carboxylate

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 1049PyridineSolvent

Conditions

Temperature
125 °C

Procedure

NaH2PO2 x H2O (2.12 g, 20.02 mmol, 8.0 equiv) and Raney nickel (1.50 g) were added at room temperature to a solution of 3-chloro-8-cyano-naphthalene-2-carboxylic acid ethyl ester (0.65 g, 2.50 mmol) in pyridine (16 ml)/AcOH (8 ml)/H2O (8 ml). The heterogeneous mixture was heated to 125° C. for 2 hours. After cooling and filtering off the Raney nickel catalyst, the reaction mixture was diluted with water (100 ml). After extraction with EtOAc (2×400 ml), the combined organic layers were washed with brine (2×50 ml), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via flash chromatography (gradient of hexane/EtOAc 100:0 to 90:10) to afford the title compound (350 mg, 53%, inseparable 1:1.5 mixture of regioisomers A:B) as a white solid. 1H NMR (400 MHz, CDCl3): δ=10.35 (s, 1H isomer B), 10.33 (s, 1H isomer A), 9.70 (s, 1H isomer B), 9.41 (s, 1H isomer A), 8.39 (s, 1H isomer A), 8.14 (d, J=8.4 Hz, 1H isomer A). 8.08 (dd, J=7.1/1.2 Hz, 1H isomer B), 8.04-8.01 (m, 1H isomer A+1H isomer B), 7.99 (1H isomer B), 7.77-7.70 (m, 1H isomer A+1H isomer B), 4.48 (q, J=7.1 Hz, 2H isomer B), 4.47 (q, J=7.1 Hz, 2H isomer A), 1.46 (t, J=7.1 Hz, 3H isomer B), 1.45 (t, J=7.1 Hz, 3H isomer A). MS (ES+): 263 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. filtrationfiltering off the Raney nickel catalyst
  3. additionthe reaction mixture was diluted with water (100 ml)
  4. extractionAfter extraction with EtOAc (2×400 ml)
  5. washthe combined organic layers were washed with brine (2×50 ml)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified via flash chromatography (gradient of hexane/EtOAc 100:0 to 90:10)

Sources & evidence

ORD record
ord-9effe3d151d549d494db3e29092598ff
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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