Hydrochloric Acid → HCID 178500110, compound

HRID 2088906Notes

Reaction equation

HRID 2088906 reaction equation
C[O-].[Na+].C[O:5][C:6](=O)[CH2:7][C:8]([O:10]C)=O.[C:13]([O:18][CH2:19]C)(=[O:17])/[CH:14]=[CH:15]/[CH3:16].C(O)(=O)C.[CH:25]([NH2:27])=[NH:26].Cl>CO.O>[OH:5][C:6]1[C:7]([CH:15]([CH3:16])[CH2:14][C:13]([O:18][CH3:19])=[O:17])=[C:8]([OH:10])[N:27]=[CH:25][N:26]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7943Dimethyl malonateHCID 160693Formamidine acetateHCID 429065Ethyl trans-crotonateHCID 10942334Sodium Methoxide2×

Product 1

HCID 178500110HCID 178500110, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
67.5 °C

Procedure

Charge anhydrous methanol (50 mL) to a flask followed by sodium methoxide (5.4 g, 0.1 mol, 0.3 equiv) and heat the mixture to 65-70° C. Add propanedioic acid dimethyl ester (44 g, 0.33 mol, 1.0 equiv) drop wise and the stir mixture at 65-70° C. for 10-30 min. Add ethyl crotonate (33.4 g, 0.33 mol, 1.0 equiv) drop wise over 1-2 h, and stir the mixture at 65-70° C. for 1-1.5 h. Cool the reaction mixture to −20° C. to −10° C. In a separate flask, dissolve sodium methoxide (54 g, 1.0 mol, 3.0 equiv) in anhydrous methanol (180 mL) and stir the mixture for 20-30 min. Cool the mixture to −20° C. to −10° C., and add formamidine acetate (40 g, 0.4 mol, 1.2 equiv). Add this solution drop wise to the first solution over a period of 1 h while maintaining the temperature from −20° C. to −10° C. Stir for 1-2 h and then warm the mixture to 20-25° C. over 3-4 h. Stir the mixture for 2-8 h, and then charge a solution of concentrated HCl (110-130 g) in water (330 g-390 g) while keeping the reaction temperature <10° C. Stir the suspension for 30-60 min at <10° C. and filter. Wash the filter cake with water (70 mL) and slurry the filter cake with methanol (56 g). Filter to collect methyl 3-(4,6-dihydroxypyrimidin-5-yl)butanoate (55.6 g, 72%). MS (ES) m/z=213 [M]+.

Workup

  1. temperatureCool the reaction mixture to −20° C. to −10° C
  2. stirringstir the mixture for 20-30 min
  3. temperatureCool the mixture to −20° C. to −10° C.
  4. additionAdd this solution drop wise to the first solution over a period of 1 h
  5. temperaturewhile maintaining the temperature from −20° C. to −10° C
  6. stirringStir for 1-2 h
  7. temperaturewarm the mixture to 20-25° C. over 3-4 h
  8. stirringStir the mixture for 2-8 h
  9. customthe reaction temperature <10° C
  10. stirringStir the suspension for 30-60 min at <10° C.
  11. filtrationfilter
  12. washWash the filter cake with water (70 mL)
  13. filtrationFilter
  14. customto collect methyl 3-(4,6-dihydroxypyrimidin-5-yl)butanoate (55.6 g, 72%)

Sources & evidence

ORD record
ord-b8ec4b8584ac434a965c9ee9eddbb803
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Reaction notes

Loading…