Acetic Acid → 2-Chloro-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester

HRID 1091946Notes

Reaction equation

HRID 1091946 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6](Cl)=[N:7][C:8]([Cl:12])=[N:9][C:10]=1[CH3:11])=[O:4].C[O-].[Na+].C[C:18](O)=[O:19]>CO>[CH3:1][O:2][C:3]([C:5]1[C:6]([O:19][CH3:18])=[N:7][C:8]([Cl:12])=[N:9][C:10]=1[CH3:11])=[O:4]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 10942334Sodium MethoxideHCID 57531614Methyl 2,4-dichloro-6-methylpyrimidine-5-carboxylate

Product 1

HCID 575314302-Chloro-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 2,4-dichloro-6-methyl-pyrimidine-5-carboxylic acid methyl ester (15.3 g, 69.6 mmol) in methanol (150 mL) at 0° C. under nitrogen with magnetic stirring is added 0.5 M NaOMe in MeOH (139 mL, 69.6 mmol) in dropwise fashion over 1 h. HOAc (2 mL) is added and the reaction mixture is evaporated at reduced pressure. The resulting residue is treated with sat. NaHCO3 (100 mL) and extracted with EtOAc (120 mL×3). The combined organic layers are washed with water (75 mL) and brine (75 mL), dried over magnesium sulfate, filtered and evaporated at reduced pressure to obtain a cream-colored solid. Purification by chromatography on silica gel (1:3 ether/hexanes) affords the title compound a s a white solid (less polar of two isomeric addition products formed) and 4-chloro-2-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester. 2-Chloro-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester 1H NMR (CDCl3) δ=4.03 (s, 3H), 3.92 (s, 3H), 2.48 (s, 3H). 4-Chloro-2-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester 1H NMR (CDCl3) δ=4.03 (s, 3H), 3.95 (s, 3H), 2.50 (s, 3H).

Workup

  1. customthe reaction mixture is evaporated at reduced pressure
  2. additionThe resulting residue is treated with sat. NaHCO3 (100 mL)
  3. extractionextracted with EtOAc (120 mL×3)
  4. washThe combined organic layers are washed with water (75 mL) and brine (75 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated at reduced pressure
  8. customto obtain a cream-colored solid
  9. customPurification by chromatography on silica gel (1:3 ether/hexanes)

Sources & evidence

ORD record
ord-419b644bebb842f882a6e15abd487158
Source dataset
uspto-grants-2012_03
Patent number
US08129395B2

Reaction notes

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