Ethyl Acetate → 6-(4-Bromo-3-formyl-phenoxy)-3-cyano-pyridine-2-carboxylic acid ethyl ester

HRID 1255654Notes

Reaction equation

HRID 1255654 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11](Br)=[CH:10][CH:9]=[C:8]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[C:16]([CH:21]=[O:22])[CH:15]=2)[N:7]=1)=[O:5])[CH3:2].[C:23]([Cu])#[N:24].C(OCC)(=O)C>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:11]([C:23]#[N:24])=[CH:10][CH:9]=[C:8]([O:13][C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[C:16]([CH:21]=[O:22])[CH:15]=2)[N:7]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 579691683-Bromo-6-(4-bromo-3-formyl-phenoxy)-pyridine-2-carboxylic acid ethyl esterHCID 178418546HCID 178418546, compound

Product 1

HCID 866364206-(4-Bromo-3-formyl-phenoxy)-3-cyano-pyridine-2-carboxylic acid ethyl esterYield 19.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-bromo-6-(4-bromo-3-formyl-phenoxy)-pyridine-2-carboxylic acid ethyl ester (23, 1.8 g, 4.19 mmol) in DMF (6 mL) was added CuCN (0.75 g, 8.38 mmol) in portions at 130° C. and heated for 4 hour. The mixture was cooled to room temperature and ethyl acetate (100 mL) was added. The mixture was stirred for 10 minutes, filtered, and washed with ethyl acetate (2×50 mL). The filtrate was washed with water (2×50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue was purified by column chromatography (25% ethyl acetate/hexanes) to yield compound 24 (0.3 g, 19%) as a white solid. 1H NMR 400 MHz (DMSO-d6) δ: 10.20 (s, 1H), 8.51 (d, J=8.6 Hz, 1H), 7.91 (d, J=8.9 Hz, 1H), 7.76 (s, 1H), 7.59 (d, J=2.7 Hz, 1H), 7.55 (dd, J=8.5, 2.7 Hz, 1H), 4.32 (q, J=7.1 Hz, 2H), 1.26 (t, J=7.0 Hz, 3H); MS (ES) m/z: 377 (M+1)+.

Workup

  1. temperatureheated for 4 hour
  2. filtrationfiltered
  3. washwashed with ethyl acetate (2×50 mL)
  4. washThe filtrate was washed with water (2×50 mL) and brine (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe residue was purified by column chromatography (25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-8005d6ada01647dc86d61ee52d12304c
Source dataset
uspto-grants-2013_06
Patent number
US08461135B2

Reaction notes

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