Diisopropylethylamine → Methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxoheptanoate

HRID 1622974Notes

Reaction equation

HRID 1622974 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=2[C:11]#[N:12])=[N:7][CH:8]=1.[O:17]=[C:18]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:19][C:20]([O:22][CH3:23])=[O:21].C(N(C(C)C)CC)(C)C.[Cl-].[Li+]>CCCCCC.C(OCC)(=O)C.O.O1CCCC1>[C:11]([C:10]1[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=1[C:6]1[N:7]=[CH:8][C:3]([CH2:2][CH:19]([C:18](=[O:17])[CH2:24][CH2:25][CH2:26][CH3:27])[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:5]=1)#[N:12]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 546075Methyl 3-oxoheptanoateHCID 193831152-[5-(Bromomethyl)pyridin-2-yl]benzonitrile

Product 1

HCID 67008908Methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxoheptanoateYield 51%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

Process 1: Under argon atmosphere, a tetrahydrofuran (900 mL) solution of 2-[5-(bromomethyl)pyridin-2-yl]benzonitrile (31.9 g, 117 mmol), methyl 3-oxoheptanoate (27.8 g, 176 mmol), diisopropylethylamine (31.0 g, 240 mmol), and lithium chloride (8.2 g, 193 mmol) was refluxed for 23 hours under heating. The reaction mixture was added water and extracted with ethyl acetate. The organic layer was combined, washed with water and brine, dried over anhydeous sodium sulfate, and concentrated in vacuo. The residues obtained were subjected to silica gel column chromatography (hexane/ethyl acetate=2:1), to obtain methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxoheptanoate (20.9 g, 51%) as a brown oil.

Workup

  1. temperatureunder heating
  2. extractionextracted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over anhydeous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residues obtained

Sources & evidence

ORD record
ord-19efd8a72bac4f2196e32241942b4fe9
Source dataset
uspto-grants-2014_07
Patent number
US08778954B2

Reaction notes

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