Sodium Carbonate → Methyl 4-(2-Chloro-5-fluoro-4-pyrimidinyl)benzoate

HRID 968694Notes

Reaction equation

HRID 968694 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.COB([C:14]1[CH:19]=[CH:18][C:17]([C:20]([OH:22])=[O:21])=[CH:16][CH:15]=1)O.[C:23]([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[CH3:23][O:22][C:20](=[O:21])[C:17]1[CH:16]=[CH:15][C:14]([C:6]2[C:5]([F:9])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)=[CH:19][CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 669046664-Carboxybenzeneboronic acid methyl ester

Product 1

HCID 85941984Methyl 4-(2-Chloro-5-fluoro-4-pyrimidinyl)benzoateYield 46%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 2,4-dichloro-5-fluoropyrimidine (0.478 g, 2.86 mmol) and 4-carboxyphenyl boronic acid methyl ester (0.516 g, 2.86 mmol) in 5 mL of ethyleneglycol dimethyl ether was added Pd(PPh3)4 under argon, followed by 2N Na2CO3 and the resulting mixture purged with argon for 2 minutes. The resulting mixture was sealed and heated at 85° C. overnight. After 18 hours, the reaction was diluted with 20 mL of ethyl acetate and washed with H2O. The organic layer was concentrated and purified by chromatography (Silica, 10% ethyl acetate in hexanes) to afford 4-(2-chloro-5-fluoropyrimidin-4-yl)-benzoic acid methyl ester (0.35 g, 46%) as a white solid. LCMS: ES+=267.

Workup

  1. customthe resulting mixture purged with argon for 2 minutes
  2. customThe resulting mixture was sealed
  3. additionthe reaction was diluted with 20 mL of ethyl acetate
  4. washwashed with H2O
  5. concentrationThe organic layer was concentrated
  6. custompurified by chromatography (Silica, 10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-278f07dca0664cd1a90f4aeb191c38d4
Source dataset
uspto-grants-2007_12
Patent number
US07304071B2

Reaction notes

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