Hydrochloric Acid → Potassium tert-butoxide

HRID 1373459Notes

Reaction equation

HRID 1373459 reaction equation
[C:1]([C:4](=[C:9](OC)[CH3:10])[C:5]([O:7][CH3:8])=[O:6])(=O)[CH3:2].C(O)(=O)C.[CH:17]([NH2:19])=[NH:18].[CH3:20][C:21]([CH3:24])([O-:23])[CH3:22].[K+:25].Cl>C1COCC1.CO.CC(C)=O>[CH3:20][C:21]([CH3:24])([O-:23])[CH3:22].[K+:25].[CH3:2][C:1]1[C:4]([C:5]([O:7][CH3:8])=[O:6])=[C:9]([CH3:10])[N:19]=[CH:17][N:18]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 160693Formamidine acetateHCID 23665647Potassium tert-butoxideHCID 58945195Methyl 2-acetyl-3-methoxybut-2-enoate

Product 2

HCID 23665647Potassium tert-butoxideHCID 29949935Methyl 4,6-dimethylpyrimidine-5-carboxylate

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Methyl 2-acetyl-3-methoxy-2-butenoate (86 g), formamidine acetate (62.5 g), acetone (344 ml) and methyl alcohol (258 ml) were charged into a 2 L 3-necked, flask (fitted with addition funnel, condenser, agitator and nitrogen inlet). The reaction is blanketed with nitrogen, the agitator is started and the batch cooled to between −5 and 0° C. While the batch was cooling, a solution of potassium t-butoxide is prepared (67.4 g in THF, 258 ml) under nitrogen. When the batch reached the correct temperature, the potassium t-butoxide solution was charged slowly keeping the temperature below 5° C. The batch was allowed to warm to about 25° C. The reaction was complete after about 1.5 hours. Concentrated hydrochloric acid was added dropwise to bring the pH to 7. The batch was concentrated under vacuum until no more volatiles were collected. Methyl t-butylether (170 ml) and water (90 ml) were charged into the reaction. The batch was agitated for about 10 minutes and the layers were then separated. The lower aqueous layer was back extracted twice, each time with 170 ml methyl t-butylether. All the upper organic layers were combined and concentrated under vacuum to afford crude methyl 4,6-dimethylpyrimidine-5-carboxylate 103 gm as an oil. The product was purified by chromatography on a silica gel column eluting with heptane/ethyl acetate (7:3) followed by crystallization from heptane, m. p. 43–45° C., 1H NMR (CDCl3): δ2.53 (6H, s, CH3), δ3.96 (3H, s, OCH3), δ8.96 (1H, s, ArH). 13H CMR (CDCl3): δ167.97, δ164.71, δ158.23, δ53.05, δ23.18. HR-MS; Calculated for C7H9N2O2, m/z=153.0664. Found 153.0667.

Workup

  1. customflask (fitted with addition funnel, condenser, agitator and nitrogen inlet)
  2. temperaturethe batch cooled to between −5 and 0° C
  3. temperatureWhile the batch was cooling
  4. customthe temperature below 5° C
  5. concentrationThe batch was concentrated under vacuum until no more volatiles
  6. customwere collected
  7. additionMethyl t-butylether (170 ml) and water (90 ml) were charged into the reaction
  8. customthe layers were then separated
  9. extractionThe lower aqueous layer was back extracted twice
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-cd12208268b74ce785951ecf6fd5db18
Source dataset
uspto-grants-2007_01
Patent number
US07161024B2

Reaction notes

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