Hydrochloric Acid → ethyl (RS)-2-(2-chloropyrimidin-5-yl)-3-methylbutanoate

HRID 1085708Notes

Reaction equation

HRID 1085708 reaction equation
N([O-])=O.[Na+].N[C:6]1[N:11]=[CH:10][C:9]([CH:12]([CH:18]([CH3:20])[CH3:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:8][N:7]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:27]>O>[Cl:27][C:6]1[N:11]=[CH:10][C:9]([CH:12]([CH:18]([CH3:20])[CH3:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:8][N:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14718745HCID 14718745, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 14718746ethyl (RS)-2-(2-chloropyrimidin-5-yl)-3-methylbutanoate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A solution of sodium nitrite (1.33 gm) in water (5 cm3) was added dropwise to a cooled solution of ethyl (RS)-2-(2-aminopyrimidin-5-yl)-3-methylbutanoate (1.08 g) in concentrated aqueous hydrochloric acid solution (14.5 cm3), the temperature of the reaction mixture being maintained at less than 5° C. during the addition. The mixture was stirred at 0° C. for 3 hours, then allowed to warm to the ambient temperature and stood for 16 hours. The mixture was then cooled in an ice bath and neutralised by dropwise addition of aqueous potassium carbonate solution (the temperature of the mixture being maintained below 4° C.). The products were extracted into dichloromethane, the organic layers being washed with water and dried over anhydrous magnesium sulphate. Removal of the solvent by evaporation under reduced pressure gave a mixture of two products which was separated by column chromatography on a silica gel support, eluting firstly with dichloromethane containing 2% by volume ethyl acetate to give ethyl (RS)-2-(2-chloropyrimidin-5-yl)- 3-methylbutanoate (0.27 g), Product A, and secondly with dichloromethane containing 10% by volume methanol to give ethyl (RS)-2-(pyrimidin-2-one-5-yl)-3-methylbutanoate, (0.34 g), Product B.

Workup

  1. temperaturethe temperature of the reaction mixture being maintained at less than 5° C. during the addition
  2. temperatureto warm to the ambient temperature
  3. waitstood for 16 hours
  4. temperatureThe mixture was then cooled in an ice bath
  5. temperaturebeing maintained below 4° C.)
  6. extractionThe products were extracted into dichloromethane
  7. washthe organic layers being washed with water
  8. dry with materialdried over anhydrous magnesium sulphate
  9. customRemoval of the solvent
  10. customby evaporation under reduced pressure
  11. customgave
  12. additiona mixture of two products which
  13. customwas separated by column chromatography on a silica gel support
  14. washeluting firstly with dichloromethane containing 2% by volume ethyl acetate

Sources & evidence

ORD record
ord-b1841951a36047fcb4c95991f93bba24
Source dataset
uspto-grants-1991_04
Patent number
US05010200

Reaction notes

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