Acetic Acid → 6-Butyl-4-methoxycarbonyl-2-methyl-5-[(4-iodophenyl)methyl]pyrimidine

HRID 373965Notes

Reaction equation

HRID 373965 reaction equation
[CH2:1]([C:5]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]([C:12]#N)[C:6]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][CH:16]=1)[CH2:2][CH2:3][CH3:4].[OH:22]O.[OH-].[Na+].C[C:27](O)=[O:28]>CO>[CH2:1]([C:5]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]([C:12]([O:28][CH3:27])=[O:22])[C:6]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([I:21])=[CH:17][CH:16]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 190188006-Butyl-5-(4-iodobenzyl)-2-methylpyrimidine-4-carbonitrile

Product 1

HCID 190187946-Butyl-4-methoxycarbonyl-2-methyl-5-[(4-iodophenyl)methyl]pyrimidineYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 306 mg 6-butyl-4-cyano-2-methyl-5-[(4-iodophenyl)methyl]pyrimidine in 6 mL methanol was added 0.885 mL (~7.81 mmol) 30% H2O2 and 0.937 mL (2.34 mmol) 2.5N NaOH. The mixture was allowed to stir for 1 hour at room temperature. To the mixture was added ~1 mL HOAc. Solvent was removed in vacuo. The crude material (409 mg) was dissolved in ~20 mL methanol. To this was added 4.0 g Amberlyst-15®. The mixture was heated to 60° for 18 hours. After cooling to room temperature, ~5 mL pyridine was added. After stirring for 1 hour, the mixture was filtered through powdered cellulose flock, stripped of solvent in vacuo, stripped from toluene to remove remaining pyridine, then was medium pressure chromatographed on silica gel using 25% EtOAc/hexane to give 152 mg of the title compound, 46% yield. R f 0.21 in 30% EtOAc/hexane, visualized by UV and ammonium molybdate/ceric sulfate stain; 1H-NMR (300 MHz, CDCl3); δ7.58 (m, 2H0, 6.81 (m, 2H), 4.12 (s, 2H), 3.87 (s, 3H), 2.75 (s, 3H), 2.67 (3 line m, 2H), 1.53 (m, 2H), 1.31 (m, 2H), 0.86 (3 line m, 3H).

Workup

  1. customSolvent was removed in vacuo
  2. dissolutionThe crude material (409 mg) was dissolved in ~20 mL methanol
  3. additionTo this was added 4.0 g Amberlyst-15®
  4. temperatureThe mixture was heated to 60° for 18 hours
  5. temperatureAfter cooling to room temperature
  6. addition~5 mL pyridine was added
  7. stirringAfter stirring for 1 hour
  8. filtrationthe mixture was filtered through powdered cellulose flock
  9. customto remove
  10. customchromatographed on silica gel using 25% EtOAc/hexane

Sources & evidence

ORD record
ord-a11be5a0fa2449c2a5efc5fa5cd0a171
Source dataset
uspto-grants-1992_11
Patent number
US05166206

Reaction notes

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