Phosphorus oxychloride → 2-Methyl-5-propyl-6-chloro-pyrimidine-4-carboxylic acid ethyl ester

HRID 965685Notes

Reaction equation

HRID 965685 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:11]([CH2:12][CH2:13][CH3:14])=[C:10](O)[N:9]=[C:8]([CH3:16])[N:7]=1)=[O:5])[CH3:2].O=P(Cl)(Cl)[Cl:19]>>[CH2:1]([O:3][C:4]([C:6]1[C:11]([CH2:12][CH2:13][CH3:14])=[C:10]([Cl:19])[N:9]=[C:8]([CH3:16])[N:7]=1)=[O:5])[CH3:2]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178439777HCID 178439777, compound

Product 1

HCID 233941042-Methyl-5-propyl-6-chloro-pyrimidine-4-carboxylic acid ethyl ester

Conditions

Temperature
85 °C

Procedure

A mixture of 2-methyl-5-propyl-6-hydroxy-pyrimidine-4-carboxylic acid ethyl ester (10 mmol) and POCl3 (25 mL) is heated at 85° C. for 4 hours. The solvent is removed in vacuo and EtOAc (40 mL) and water (30 mL) are added to the residue. NaHCO3 is carefully added until the pH of aqueous layer is greater than 7. The layers are separated and the aqueous layer is extracted with EtOAc (2×30 mL). The combined extracts are washed with brine (50 mL), dried (Na2SO4), and evaporated. Flash column purification of the residue with 3:1 EtOAc, hexane provides 2-methyl-5-propyl-6-chloro-pyrimidine-4-carboxylic acid ethyl ester as a light yellow oil. Step 4. Preparation of 2-Methyl-5-propyl-4-chloromethyl-6-chloro-pyrimidine

Workup

  1. customThe solvent is removed in vacuo and EtOAc (40 mL) and water (30 mL)
  2. additionare added to the residue
  3. additionNaHCO3 is carefully added until the pH of aqueous layer
  4. customThe layers are separated
  5. extractionthe aqueous layer is extracted with EtOAc (2×30 mL)
  6. washThe combined extracts are washed with brine (50 mL)
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customFlash column purification of the residue with 3:1 EtOAc, hexane

Sources & evidence

ORD record
ord-517ddb9926014f848dd7403fe75c1b53
Source dataset
uspto-grants-2005_10
Patent number
US06951864B2

Reaction notes

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