Methanol → 2-Chloro-5-fluoro-4-methoxy-6-methylpyrimidine

HRID 521698Notes

Reaction equation

HRID 521698 reaction equation
[CH3:1][O-:2].[Na+].[Cl:4][C:5]1[N:10]=[C:9](Cl)[C:8]([F:12])=[C:7]([CH3:13])[N:6]=1.CO.O>ClCCl>[Cl:4][C:5]1[N:10]=[C:9]([O:2][CH3:1])[C:8]([F:12])=[C:7]([CH3:13])[N:6]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 10942334Sodium MethoxideHCID 249035132,4-Dichloro-5-fluoro-6-methylpyrimidine

Product 1

HCID 582523322-Chloro-5-fluoro-4-methoxy-6-methylpyrimidineYield 87.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sodium methoxide (446.53 mg, 8.27 mmol) is added portion wise to a stirred solution of 2,4-dichloro-5-fluoro-6-methyl-pyrimidine (1.7 g, 7.51 mmol) in methanol (8 mL, 197.66 mmol) at 0° C. The mixture is then stirred at room temperature for 1 hour. Water (20 mL) is added to the reaction mixture followed by dichloromethane. The layers are separated and the aqueous layer is re-extracted with dichloromethane. The combined organic extracts are dried over magnesium sulfate and the solvents are evaporated under reduced pressure to give an 8:1 of mixture of product to starting material. The crude material is purified by silica gel chromatography using a 0-99% gradient of dichloromethane in iso-hexanes to give the title compound (1.16 g, 87%). 1H NMR (CDCl3) δ 4.09 (s, 3H), 2.45 (d, 3H).

Workup

  1. customThe layers are separated
  2. extractionthe aqueous layer is re-extracted with dichloromethane
  3. dry with materialThe combined organic extracts are dried over magnesium sulfate
  4. customthe solvents are evaporated under reduced pressure
  5. customto give
  6. additionan 8:1 of mixture of product
  7. customThe crude material is purified by silica gel chromatography

Sources & evidence

ORD record
ord-21689a34b36e44a5920296e05459566b
Source dataset
uspto-grants-2016_05
Patent number
US09328124B2

Reaction notes

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