Cesium carbonate → 5-Cyclopropyl-6-methyl-pyridine-2-carbonitrile

HRID 624849Notes

Reaction equation

HRID 624849 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:9]#[N:10])=[N:6][C:7]=1[CH3:8].[CH:11]1(B(O)O)[CH2:13][CH2:12]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:11]1([C:2]2[CH:3]=[CH:4][C:5]([C:9]#[N:10])=[N:6][C:7]=2[CH3:8])[CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 2760897Cyclopropylboronic acidHCID 498187795-Bromo-6-methylpyridine-2-carbonitrile

Product 1

HCID 866747695-Cyclopropyl-6-methyl-pyridine-2-carbonitrileYield 75.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

5-Bromo-6-methyl-pyridine-2-carbonitrile (0.5 g, 2.5 mmol), cyclopropylboronic acid (CAN 411235-57-9, 0.36 g, 4 mmol), Pd2(dba)3 (CAN 411235-57-9, 0.1 g, 0.2 mmol), xantphos (CAN 161265-03-8, 0.15 g, 0.26 mmol) and Cs2CO3 (1.1 g, 3 mmol) were suspended in 1,4-dioxane (30 mL) under a nitrogen atmosphere. The mixture was stirred for 12 h at 110° C., filtered, concentrated under reduced pressure and purified by column chromatography (silica gel, 5 g, eluting with 10% ethyl acetate in petroleum ether) to give the title compound (0.3 g, 75%) as yellow solid; MS (EI): m/e=159.2 [M+H]+.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated under reduced pressure
  3. custompurified by column chromatography (silica gel, 5 g, eluting with 10% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-ab35420612014f9dac7f8e9f199c4330
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Reaction notes

Loading…