4,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide → 1-[4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]-1-propanone

HRID 2255405Notes

Reaction equation

HRID 2255405 reaction equation
[CH3:1][C:2]([C:5]1[C:10]([OH:11])=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[N:8]=[C:7]([C:16](N(OC)C)=[O:17])[N:6]=1)([CH3:4])[CH3:3].[CH2:22]([Mg]Br)[CH3:23]>O1CCCC1.C(OCC)C>[CH3:13][C:12]([C:9]1[C:10]([OH:11])=[C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])[N:6]=[C:7]([C:16](=[O:17])[CH2:22][CH3:23])[N:8]=1)([CH3:14])[CH3:15]

Participants

5

Reactant 2

HCID 100401704,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamideHCID 178418443HCID 178418443, compound

Product 1

HCID 104229331-[4,6-Bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinyl]-1-propanone

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 8.4 g (28 mmol) of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide in 150 mL of tetrahydrofuran was cooled in ice and treated dropwise with 40 mL (120 mmol) of a 3.0M solution of ethylmagnesium bromide in diethyl ether. The mixture was stirred in ice for 2 hours, then at room temperature for an additional 16 hours. The reaction mixture was again cooled in ice, and excess Grignard reagent was destroyed by dropwise addition of 50 mL of saturated aqueous ammonium chloride solution. The reaction mixture was added to 400 mL of ammonium chloride solution and extracted several times with ethyl acetate. The combined organic layers were washed with brine, dried (anhydrous sodium sulfate), and evaporated. Recrystallization of the residue from hexane yielded 5.0 g (67%) of the ethyl ketone product, mp 123° C.-125° C.

Workup

  1. waitat room temperature for an additional 16 hours
  2. temperatureThe reaction mixture was again cooled in ice
  3. customexcess Grignard reagent was destroyed by dropwise addition of 50 mL of saturated aqueous ammonium chloride solution
  4. additionThe reaction mixture was added to 400 mL of ammonium chloride solution
  5. extractionextracted several times with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried (anhydrous sodium sulfate)
  8. customevaporated
  9. customRecrystallization of the residue from hexane
  10. customyielded 5.0 g (67%) of the ethyl ketone product, mp 123° C.-125° C.

Sources & evidence

ORD record
ord-86889ee9df6449fa8a3fd7e91e128b34
Source dataset
uspto-grants-1993_08
Patent number
US05240929

Reaction notes

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