Isoamyl Nitrite → 4,6-Bis(1,1-dimethylethyl)-5-[(2-methoxyethoxy)methoxy]-2-pyrimidinecarboxaldehyde oxime

HRID 1707972

Reaction equation

HRID 1707972 reaction equation
[Na].[CH3:2][C:3]([C:6]1[C:11]([O:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH3:18])=[C:10]([C:19]([CH3:22])([CH3:21])[CH3:20])[N:9]=[C:8]([CH3:23])[N:7]=1)([CH3:5])[CH3:4].[N:24](OCCC(C)C)=[O:25].[Cl-].[NH4+]>N.O1CCCC1>[CH3:5][C:3]([C:6]1[C:11]([O:12][CH2:13][O:14][CH2:15][CH2:16][O:17][CH3:18])=[C:10]([C:19]([CH3:22])([CH3:21])[CH3:20])[N:9]=[C:8]([CH:23]=[N:24][OH:25])[N:7]=1)([CH3:2])[CH3:4]

Participants

7

Reactant 4

HCID 8053Isoamyl NitriteHCID 25517Ammonium ChlorideHCID 5360545SodiumHCID 199229904,6-Ditert-butyl-5-[(2-methoxyethoxy)methoxy]-2-methylpyrimidine

Product 1

HCID 1363784124,6-Bis(1,1-dimethylethyl)-5-[(2-methoxyethoxy)methoxy]-2-pyrimidinecarboxaldehyde oximeYield 21.3%

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

Sodium metal (0.28 g, 12.6 mmoles) is dissolved in 50 mL of freshly distilled ammonia at reflux under argon. The reaction mixture is stirred at reflux until the solution turns light gray. 4,6-Bis(1,1-dimethylethyl)-5-[(2-methoxyethoxy)-methoxy]-2-methyl-pyrimidine (3.0 g, 9.7 mmoles) is dissolved in 20 mL of tetrahydrofuran and added to the reaction. After 10 minutes, isoamyl nitrite (2.3 g, 19.3 mmoles) is added, and the reaction mixture is stirred at reflux for 2 hours. It is quenched by the addition of ammonium chloride (1.0 g, 18.7 mmoles) and the ammonia is allowed to evaporate at room temperature. The remaining oil is partitioned between 50 mL of ethyl acetate and 50 mL of water. The organic layer is washed with water (3×50 mL) and brine (50 mL), dried over magnesium sulfate, and the solvent is evaporated. The crude product is adsorbed onto a silica gel plug which is eluted with 300 mL of 5% ether in chloroform, followed by 300 mL of ether. Evaporation of the ether eluant gives 4,6-bis (1,1-dimethylethyl)-5-[(2-methoxyethoxy)methoxy]-2-pyrimidine-carboxaldehyde oxime (0.7 g, 21%) , mp 90°-97° C.

Workup

  1. temperatureat reflux under argon
  2. temperatureat reflux until the solution
  3. additionadded to the reaction
  4. stirringthe reaction mixture is stirred
  5. temperatureat reflux for 2 hours
  6. customto evaporate at room temperature
  7. customThe remaining oil is partitioned between 50 mL of ethyl acetate and 50 mL of water
  8. washThe organic layer is washed with water (3×50 mL) and brine (50 mL)
  9. dry with materialdried over magnesium sulfate
  10. customthe solvent is evaporated
  11. washis eluted with 300 mL of 5% ether in chloroform
  12. customEvaporation of the ether eluant

Sources & evidence

ORD record
ord-95716d4a08dc4e5498b78c273bd2adcd
Source dataset
uspto-grants-1994_10
Patent number
US05356898

Linked notes

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