Dimethylformamide → HCID 69743557, compound

HRID 1760362Notes

Reaction equation

HRID 1760362 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:10][CH2:9][CH2:8][N:7]1[C:11]1[CH:12]=[N:13][C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=2)=[CH:15][CH:16]=1)=[O:5])[CH3:2].[CH3:30][N:31](C)C=O>C1(C)C=CC=CC=1.[C-]#N.[Zn+2].[C-]#N>[CH2:1]([O:3][C:4]([C:6]1([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:10][CH2:9][CH2:8][N:7]1[C:11]1[CH:12]=[N:13][C:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([C:30]#[N:31])=[CH:20][CH:19]=2)=[CH:15][CH:16]=1)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 12133937HCID 12133937, compound

Product 1

HCID 69743557HCID 69743557, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-[6-(4-bromo-phenoxy)-pyridin-3-yl]-pyrrolidine-2,2-dicarboxylic acid diethyl ester (0.28 g, 0.53 mmol), zinc cyanide (0.037 g, 0.32 mmol), tetrakistriphenylphosphine palladium (0) (0.024 g, 0.021 mmol) and 0.66 mL of dimethylformamide was heated to 80° C. for 24 hours. An additional 37 mg of zinc cyanide and 24 mg of tetrakistriphenylphosphine palladium (0) was added and the mixture was stirred at 80° C. for an additional 48 hours. After cooling to room temperature, the mixture was diluted with toluene and was washed with 2M ammonium hydroxide (twice), brine, dried over sodium sulphate, filtered and concentrated in vacuo. Purification by radial chromatography (ethyl acetate-hexanes, then methanol) afforded 58 mg of 1-[6-(4-Cyano-phenoxy)-pyridin-3-yl]-pyrrolidine-2,2-dicarboxylic acid diethyl ester as a colorless syrup. 1H NMR (CDCl3, 500 MHz): 8.07 (d, 1H, J=3.5 Hz), 7.80 (dd, 1H, J=2.5, 9.0 Hz), 7.69 (d, 2H, J=9.0 Hz), 7.25 (d, 2H, J=9.0 Hz), 7.02 (d, 1H, J=9.0 Hz), 4.21 (q, 4H, J=7.5 Hz), 2.74 (m, 2H), 2.66 (m, 2H), 1.19 (t, 6H, J=7.0 Hz) ppm. MS (APCl, m/z): 424 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwas washed with 2M ammonium hydroxide (twice), brine
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by radial chromatography (ethyl acetate-hexanes

Sources & evidence

ORD record
ord-8eae9ea284cf4ec4b21ce445a6055dda
Source dataset
uspto-grants-2005_01
Patent number
US06841671B2

Reaction notes

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