Sodium Carbonate → 2-chloro-4-(2-fluoropyridin-4-yl)pyrimidine

HRID 1774147Notes

Reaction equation

HRID 1774147 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[F:7][C:8]1[CH:13]=[C:12](B(O)O)[CH:11]=[CH:10][N:9]=1.[Cl:17][C:18]1[N:23]=[C:22](Cl)[CH:21]=[CH:20][N:19]=1>O1CCOCC1.O.O.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]>[Cl:17][C:18]1[N:23]=[C:22]([C:12]2[CH:11]=[CH:10][N:9]=[C:8]([F:7])[CH:13]=2)[CH:21]=[CH:20][N:19]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 775312,4-DichloropyrimidineHCID 27833962-Fluoropyridine-4-boronic acid

Product 1

HCID 6405362-chloro-4-(2-fluoropyridin-4-yl)pyrimidineYield 96.8%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

Sodium carbonate (4.91 g, 46.3 mmol) was added to 2-fluoropyridin-4-ylboronic acid (2.61 g, 18.5 mmol) and 2,4-dichloropyrimidine (77.2 mL, 15.4 mmol) in dioxane/water (77 mL, 4:1), and the suspension was purged with argon. PdCl2(dppf)*DCM (0.630 g, 0.772 mmol) was added to the mixture, and the mixture was heated at 80° C. under argon. After 3 hours, the reaction mixture was diluted with water, and the resulting solid was collected by vacuum filtration to yield 2-chloro-4-(2-fluoropyridin-4-yl)pyrimidine (3.12 g, 14.9 mmol, 96.4% yield) with minor impurities.

Workup

  1. customthe suspension was purged with argon
  2. filtrationthe resulting solid was collected by vacuum filtration

Sources & evidence

ORD record
ord-9c5764f03de44ad2831e29fab91c5845
Source dataset
uspto-grants-2016_02
Patent number
US09259470B2

Reaction notes

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