Cesium carbonate → 5-Cyclopropyl-6-(4-fluoro-benzyl)-pyridine-2-carbonitrile

HRID 632204Notes

Reaction equation

HRID 632204 reaction equation
Br[CH2:2][C:3]1[N:8]=[C:7]([C:9]#[N:10])[CH:6]=[CH:5][C:4]=1[CH:11]1[CH2:13][CH2:12]1.[F:14][C:15]1[CH:24]=[CH:23][C:18](CB(O)O)=[CH:17][CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH:11]1([C:4]2[CH:5]=[CH:6][C:7]([C:9]#[N:10])=[N:8][C:3]=2[CH2:2][C:18]2[CH:23]=[CH:24][C:15]([F:14])=[CH:16][CH:17]=2)[CH2:13][CH2:12]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 45090593(4-Fluorobenzyl)boronic acidHCID 866747706-Bromomethyl-5-cyclopropyl-pyridine-2-carbonitrile

Product 1

HCID 710874595-Cyclopropyl-6-(4-fluoro-benzyl)-pyridine-2-carbonitrileYield 79.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-bromomethyl-5-cyclopropyl-pyridine-2-carbonitrile (0.1 g, 0.4 mmol), 4-fluoro-benzylboronic acid (CAN 1765-93-1, 0.1 g, 0.7 mmol), Pd(dppf)Cl2 (CAN 95464-05-4, 50 mg, 0.068 mmol), Cs2CO3 (0.2 g, 0.6 mmol) in 1.4-dioxane (10 mL) was stirred for 12 h at 110° C. under a nitrogen atmosphere. The mixture was filtered, concentrated and purified by flash column chromatography (silica gel, 3 g, eluting with 25% ethyl acetate in petroleum ether) to give the title compound (80 mg, 75%) as yellow solid; MS (EI): m/e=253.2 [M+H]+.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. custompurified by flash column chromatography (silica gel, 3 g, eluting with 25% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-7a983094d73a4059bd0fa23a9685c3b8
Source dataset
uspto-grants-2016_04
Patent number
US09321727B2

Reaction notes

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