Hydrochloric Acid → 6-Ethylpyrimidin-4-ol

HRID 964953Notes

Reaction equation

HRID 964953 reaction equation
C[O-].[Na+].C(O)(=O)C.[CH:8]([NH2:10])=[NH:9].[C:11]([CH2:15][C:16](OC)=[O:17])(=O)[CH2:12][CH3:13].Cl>CO>[CH2:12]([C:11]1[N:10]=[CH:8][NH:9][C:16](=[O:17])[CH:15]=1)[CH3:13]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 121699Methyl 3-oxovalerateHCID 160693Formamidine acetateHCID 10942334Sodium Methoxide

Product 1

HCID 1354076886-Ethylpyrimidin-4-ol

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of sodium methoxide (4.19 kg, 77.6 mol) and formamidine acetate (3.0 kg, 28.8 mol) in methanol (45 L) at 5°-10° C. was added slowly a solution of methyl propionylacetate (2.5 kg, 19.2 mol) in methanol (10 L) maintaining the temperature below 20° C. throughout the addition. The resulting mixture was stirred at room temperature overnight after which time the pH was adjusted to 7 by the addition of concentrated hydrochloric acid. The reaction mixture was concentrated under reduced pressure to ca. 10 L in volume, diluted with water (10 L) and was extracted with 2-butanone (2×30 L). The combined organic extracts were concentrated under reduced pressure to ca. 2 L in volume and diluted with ethyl acetate (4 L). The desired product crystallised from the solution (2,4 kg, 70%) and was recrystallised from isopropanol to yield a product of m.p. 132°-134° C. Found: C,58.45; H,6.37; N,22.41; C6H8N2O requires: C,58.05; H,6.50; N,22.57%.

Workup

  1. temperaturemaintaining the temperature below 20° C.
  2. additionthroughout the addition
  3. concentrationThe reaction mixture was concentrated under reduced pressure to ca. 10 L in volume
  4. additiondiluted with water (10 L)
  5. extractionwas extracted with 2-butanone (2×30 L)
  6. concentrationThe combined organic extracts were concentrated under reduced pressure to ca. 2 L in volume
  7. additiondiluted with ethyl acetate (4 L)
  8. customThe desired product crystallised from the solution (2,4 kg, 70%)
  9. customwas recrystallised from isopropanol
  10. customto yield a product of m.p. 132°-134° C

Sources & evidence

ORD record
ord-273fbc415a674edab68fb1eec2dd2ff2
Source dataset
uspto-grants-1998_06
Patent number
US05773443

Reaction notes

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