N,N-Diethylaniline → 4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester

HRID 1696437Notes

Reaction equation

HRID 1696437 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](O)=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2].O=P(Cl)(Cl)[Cl:17].CCN(C1C=CC=CC=1)CC>>[CH2:1]([O:3][C:4]([C:6]1[C:7]([Cl:17])=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2]

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178418871HCID 178418871, compound

Product 1

HCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterYield 77,136.703%

Procedure

A mixture of 4-hydroxy-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester (50 g, 0.234 mmol), POCl3 (110 mL, 1.17 mmol) and diethylaniline (70 mL, 0.28 mmol) was refluxed for 5 h. The solvent was removed under vacuum and the residue was dissolved in ice H2O and cautiously neutralized with aqueous NaHCO3. After extraction with EtOAc (3×400 mL), the organic extracts were combined, dried and concentrated to give 4-chloro-2-(methylsulfanyl)pyrimidine-5-carboxylic acid ethyl ester as a yellow solid (42 g, 77% yield). 1H NMR (300 MHz, CDCl3): δ 8.92 (s, 1H), 4.41 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H).

Workup

  1. temperaturewas refluxed for 5 h
  2. customThe solvent was removed under vacuum
  3. dissolutionthe residue was dissolved in ice H2O
  4. extractionAfter extraction with EtOAc (3×400 mL)
  5. customdried
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-43b7e8659e274ef9acceffe79f2ca5a4
Source dataset
uspto-grants-2012_04
Patent number
US08163756B2

Reaction notes

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