Cesium fluoride → 2-(4-Cyanonaphthalene-2-yl)isonicotinic acid ethyl ester

HRID 2383342Notes

Reaction equation

HRID 2383342 reaction equation
[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[C:5](B(O)O)[CH:4]=1)#[N:2].[CH2:16]([O:18][C:19](=[O:27])[C:20]1[CH:25]=[CH:24][N:23]=[C:22](Br)[CH:21]=1)[CH3:17].[F-].[Cs+]>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:16]([O:18][C:19](=[O:27])[C:20]1[CH:21]=[CH:22][N:23]=[C:24]([C:5]2[CH:4]=[C:3]([C:1]#[N:2])[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[CH:6]=2)[CH:25]=1)[CH3:17]

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 3847769Ethyl 2-bromoisonicotinateHCID 67309212(4-Cyanonaphthalen-2-yl)boronic acid

Product 1

HCID 673092232-(4-Cyanonaphthalene-2-yl)isonicotinic acid ethyl esterYield 91.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a suspension of 4-cyano-2-naphthaleneboronic acid (0.10 g), 2-bromoisonicotinic acid ethyl ester (0.12 g) and cesium fluoride (0.09 g) in dimethoxyethane (6 mL) was added tetrakis(triphenylphosphine)palladium (0.06 g), and the mixture was stirred at 150° C. for 40 minutes using microwave reactor (Biotage). The reaction mixture was filtered through a Celite pad, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=100/0-66/34) to give 2-(4-cyanonaphthalene-2-yl)isonicotinic acid ethyl ester (0.14 g). To a solution of this compound (0.14 g) in a mixed solvent of tetrahydrofuran (4 mL), ethanol (1 mL) and water (1 mL) was added lithium hydroxide monohydrate (0.060 g), and the mixture was stirred at room temperature overnight. To the reaction mixture was added acetic acid (0.27 mL). The precipitated solid was collected by filtration, and washed with water and n-hexane. The solid was dried under reduced pressure to give the title compound (0.098 g).

Workup

  1. filtrationThe reaction mixture was filtered through a Celite pad
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=100/0-66/34)

Sources & evidence

ORD record
ord-f491c241b09444749044ec1d5197a269
Source dataset
uspto-grants-2012_09
Patent number
US08263622B2

Reaction notes

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