(3-Methoxyphenyl)boronic acid → 2-(3-Methoxy-phenyl)-pyrimidine-5-carboxylic acid methyl ester

HRID 2381964Notes

Reaction equation

HRID 2381964 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8](SC)=[N:9][CH:10]=1)=[O:4].[CH3:13][O:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[CH:19][CH:20]=1>S1C=CC=C1C([O-])=O.[Cu+].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH3:13])[CH:20]=2)=[N:9][CH:10]=1)=[O:4]

Participants

5

Reactant 2

HCID 2734370(3-Methoxyphenyl)boronic acidHCID 11194721Methyl 2-(Methylthio)pyrimidine-5-carboxylate

Product 1

HCID 685580872-(3-Methoxy-phenyl)-pyrimidine-5-carboxylic acid methyl esterYield 35.6%

Reagents, catalysts & solvents 2

HCID 11194830Cuprous 2-thiophenecarboxylateCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
85 °C

Procedure

2-Methylsulfanyl-pyrimidine-5-carboxylicacid methyl ester (323 mg, 1.75 mmol), Copper(I) thiophene-2-carboxylate (501 mg, 2.63 mmol), tetrakis(triphenylphosphine) palladium(0) (202 mg, 0.175 mmol) and 3-methoxyphenylboronic acid (400 mg, 2.63 mmol) are taken in a glass tube, evacuated, refilled with N2, added anhydrous THF (6 mL) and is heated overnight at 85° C. after closing with a cap. The reaction is cooled to rt, diluted with EtOAc and ammonium hydroxide is added. The organic layer is seperated, dried (MgSO4), filtered and concentrated in vacuo. The residue is purified by flash silica gel chromatography to afford 2-(3-methoxy-phenyl)-pyrimidine-5-carboxylic acid methyl ester (152 mg) as a powder. MS: 245 (M+H); 1H NMR (CDCl3): δ 4.00 (s, 3H), 4.82 (d, 2H), 7.55 (m, 2H), 8.46 (m, 1H), 8.53 (s, 1H), 9.33 (s, 2H).

Workup

  1. customevacuated
  2. additionrefilled with N2
  3. additionadded anhydrous THF (6 mL)
  4. temperatureThe reaction is cooled to rt
  5. additiondiluted with EtOAc and ammonium hydroxide
  6. additionis added
  7. customThe organic layer is seperated
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue is purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-b825e82c44b54f2185f7bf4d56e5402f
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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