Cesium carbonate → 4-(4-Chloro-2-fluorophenyl)-2-methylnicotinaldehyde

HRID 870961Notes

Reaction equation

HRID 870961 reaction equation
Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([CH3:10])[N:5]=[CH:4][CH:3]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[C:14]([F:21])[CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CCOC(C)=O.O.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>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([C:2]2[C:7]([CH:8]=[O:9])=[C:6]([CH3:10])[N:5]=[CH:4][CH:3]=2)=[C:14]([F:21])[CH:13]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 72211849HCID 72211849, compound

Product 1

HCID 866959504-(4-Chloro-2-fluorophenyl)-2-methylnicotinaldehydeYield 93.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-chloro-2-methylnicotinaldehyde (100 mg, 0.643 mmol), (4-chloro-2-fluorophenyl)boronic acid (123 mg, 0.707 mmol), Cs2CO3 (628 mg, 1.928 mmol) and Pd(Ph3P)4 (52.0 mg, 0.045 mmol) in toluene (5 mL) was heated at 90° C. for 16 h. After cooling, the reaction mixture was diluted with EtOAc (10 mL) and water (10 mL). The ethyl acetate layer was concentrated and purified by silica gel chromatography (2:1 Hexane-EtOAc) to afford 4-(4-chloro-2-fluorophenyl)-2-methylnicotinaldehyde (0.15 g, 0.601 mmol, 35% yield) as a yellow solid. LCMS (ESI) m/e 250.04 [(M+H)+, calcd for C13H10ClFNO 250.0]; LC/MS retention time (Method G): tR=0.96 min.

Workup

  1. temperatureAfter cooling
  2. concentrationThe ethyl acetate layer was concentrated
  3. custompurified by silica gel chromatography (2:1 Hexane-EtOAc)

Sources & evidence

ORD record
ord-405e9c7df1454d83a101e2de081c2133
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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