Hydrochloric Acid → Potassium tert-butoxide

HRID 1373463Notes

Reaction equation

HRID 1373463 reaction equation
[C:1]([C:4](=[C:9](OC)[CH3:10])[C:5]([O:7][CH3:8])=[O:6])(=O)[CH3:2].Cl.[C:14]([NH2:22])(=[NH:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[CH3:23][C:24]([CH3:27])([O-:26])[CH3:25].[K+:28].Cl>C1COCC1.CO.CC(C)=O>[CH3:23][C:24]([CH3:27])([O-:26])[CH3:25].[K+:28].[CH3:2][C:1]1[C:4]([C:5]([O:7][CH3:8])=[O:6])=[C:9]([CH3:10])[N:22]=[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:21]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 80289Benzamidine, hydrochlorideHCID 23665647Potassium tert-butoxideHCID 58945195Methyl 2-acetyl-3-methoxybut-2-enoate

Product 2

HCID 23665647Potassium tert-butoxideHCID 58781565Methyl 4,6-dimethyl-2-phenylpyrimidine-5-carboxylate

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Methyl 2-acetyl-3-methoxy-2-butenoate (34.4 g, 0.2 mole), benzamidine hydrochloride (37.4 g), acetone (136 ml) and methyl alcohol (100 ml) were charged into a 1 L 3-necked, flask (fitted with addition funnel, condenser, agitator and nitrogen inlet). The reaction was blanketed with nitrogen, the agitator started and the batch cooled to between −5 and 0°C. While the batch was cooling, a solution of potassium t-butoxide was prepared (27 g in THF, 100 ml) under nitrogen. When the batch had 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 charged dropwise to bring the pH to 7. The batch was concentrated under vacuum until no more volatiles were collected. Methyl t-butylether (300 ml), 150 ml ethyl acetate and water (200 ml) were charged. The batch was agitated for 10 minutes, a small amount of solid was filtered off, and the layers were then separated. The organic layer was concentrated under vacuum to afford a solid residue of methyl 4,6-dimethyl-2-phenylpyrimidine-5-carboxylate, 48.7 g. m. p. 54–55° C., 1H NMR (CDCl3): δ2.58 (6H, s, CH3), δ3.89 (3H, s, OCH3), δ7.42 (3H, s, ArH), δ8.40 (2H, s, ArH). 13H CMR (CDCl3): δ168.78, δ165.24, δ164.11, δ137.57, δ131.34, δ128.93, δ128.92, δ124.12, δ52.86, δ23.65. HR-MS; Calculated for C14H15N2O2, m/z=243.1134. Found 243.1134.

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 (300 ml), 150 ml ethyl acetate and water (200 ml) were charged
  8. filtrationa small amount of solid was filtered off
  9. customthe layers were then separated
  10. concentrationThe organic layer was concentrated under vacuum

Sources & evidence

ORD record
ord-3f2d46e6e1a24edfb4752ebefccef613
Source dataset
uspto-grants-2007_01
Patent number
US07161024B2

Reaction notes

Loading…