Dimethylformamide → 4,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamide

HRID 1033758Notes

Reaction equation

HRID 1033758 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](O)=[O:17])[N:6]=1)([CH3:4])[CH3:3].CN(C)C=O.C(Cl)(=O)C(Cl)=O.Cl.[CH3:31][NH:32][O:33][CH3:34].CN1CCCCC1>ClCCl>[CH3:15][C:12]([C:9]1[C:10]([OH:11])=[C:5]([C:2]([CH3:4])([CH3:1])[CH3:3])[N:6]=[C:7]([C:16]([N:32]([O:33][CH3:34])[CH3:31])=[O:17])[N:8]=1)([CH3:14])[CH3:13]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 12291N-MethylpiperidineHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 152753184,6-Ditert-butyl-5-hydroxy-2-pyrimidinecarboxylic acid

Product 1

HCID 100401704,6-Bis(1,1-dimethylethyl)-5-hydroxy-N-methoxy-N-methyl-2-pyrimidinecarboxamideYield 65.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A mixture of 8.4 g (33 mmol) of 4,6-bis(1,1-dimethylethyl)-5-hydroxy-2-pyrimidinecarboxylic acid and 0.50 mL (0.47 g, 6.5 mmol) of N,N-dimethyl formamide in 120 mL of dichloromethane was cooled in ice and treated dropwise with a solution of 4.9 mL (7.1 g, 56 mmol) of oxalyl chloride in 18 mL of dichloromethane. The mixture was stirred with ice cooling for 2 hours, then filtered, and evaporated. The residual crude acid chloride was redissolved in 85 mL of dichloromethane and added dropwise to an ice cooled mixture of 4.0 g (41 mmol) of N,O dimethylhydroxylamine hydrochloride and 15 mL (12.2 g, 123 mmol) of 1 methylpiperidine in 150 mL of dichloromethane. The mixture was stirred at room temperature for 16 hours, then washed with 0.4 N hydrochloric acid, brine, 5% aqueous sodium bicarbonate, and brine again. The organic layer was dried (anhydrous sodium sulfate) and evaporated, and the residue recrystallized from ethyl acetate/hexane to yield 6.4 g (65%) of the amide product, mp 140° C.-142° C.

Workup

  1. temperaturewas cooled in ice
  2. filtrationfiltered
  3. customevaporated
  4. dissolutionThe residual crude acid chloride was redissolved in 85 mL of dichloromethane
  5. additionadded dropwise to an ice
  6. temperaturecooled
  7. stirringThe mixture was stirred at room temperature for 16 hours
  8. washwashed with 0.4 N hydrochloric acid, brine, 5% aqueous sodium bicarbonate, and brine again
  9. dry with materialThe organic layer was dried (anhydrous sodium sulfate)
  10. customevaporated
  11. customthe residue recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-8dd74497adf14f4c8ccc71be1ac350e1
Source dataset
uspto-grants-1994_05
Patent number
US05312821

Reaction notes

Loading…