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

HRID 629044Notes

Reaction equation

HRID 629044 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][CH3:26])[CH2:19][C:20]([O:22][CH3:23])=[O:21].C(N(C(C)C)CC)(C)C.O.[Br-].[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][CH3:26])[C:20]([O:22][CH3:23])=[O:21])=[CH:4][CH:5]=1)#[N:12]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 121700Methyl 3-oxohexanoateHCID 193831152-[5-(Bromomethyl)pyridin-2-yl]benzonitrileHCID 23702478Lithium bromide hydrate

Product 1

HCID 86707837Methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxohexanoateYield 91.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Process 1: Under argon atmosphere, tetrahydrofuran (20 mL) mixture containing 2-[5-(bromomethyl)pyridin-2-yl]benzonitrile (1.1 g, 3.9 mmol), methyl 3-oxohexanoate (0.68 g, 4.7 mmol), diisopropylethylamine (1.0 g, 7.8 mmol), and lithium bromide monohydrate (0.49 g, 4.7 mmol) was refluxed under heating for 18 hours. The reaction mixture was added water and extracted three times with chloroform. 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 (SNAP100HP manufactured by Biotage) (hexane/ethyl acetate; 5/1→1/1) to give methyl 2-{[6-(2-cyanophenyl)pyridin-3-yl]methyl}-3-oxohexanoate (1.2 g, 91%) as yellow oil.

Workup

  1. temperaturewas refluxed
  2. temperatureunder heating for 18 hours
  3. extractionextracted three times with chloroform
  4. washwashed with water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8f18c63747da42a6ac30a43b80ef1485
Source dataset
uspto-grants-2016_04
Patent number
US09315493B2

Reaction notes

Loading…