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

HRID 629040Notes

Reaction equation

HRID 629040 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+]>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

7

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 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Process 1: Under argon atmosphere, 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 under heating for 23 hours. The reaction mixture was added water and extracted with ethyl acetate. The organic layer was combined, washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The obtained residues were subjected to silica gel column chromatography (hexane/ethyl acetate=2:1) to give methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxoheptanoate (20.9 g, 51%) as brown oil.

Workup

  1. temperatureunder heating for 23 hours
  2. extractionextracted with ethyl acetate
  3. washwashed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c59dca10537a4f5b8a1481ee138bc316
Source dataset
uspto-grants-2016_04
Patent number
US09315493B2

Reaction notes

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