Ethyl 4-hydroxy-2-methylpyrimidine-5-carboxylate → 1-[2-(2,5-Dimethyl-3-furyl)-2-oxoethyl]-2-methyl-5-ethoxycarbonylpyrimid-6-one

HRID 1699361Notes

Reaction equation

HRID 1699361 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:13])[NH:8][C:9]([CH3:12])=[N:10][CH:11]=1)=[O:5])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-].Br[CH2:33][C:34]([C:36]1[CH:40]=[C:39]([CH3:41])[O:38][C:37]=1[CH3:42])=[O:35]>COCCOC>[CH3:42][C:37]1[O:38][C:39]([CH3:41])=[CH:40][C:36]=1[C:34](=[O:35])[CH2:33][N:8]1[C:7](=[O:13])[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:11][N:10]=[C:9]1[CH3:12]

Participants

5

Reactant 3

HCID 293750Ethyl 4-hydroxy-2-methylpyrimidine-5-carboxylateHCID 2724141Tetrabutylammonium FluorideHCID 186138692-Bromo-1-(2,5-dimethylfuran-3-yl)ethan-1-one

Product 1

HCID 183198911-[2-(2,5-Dimethyl-3-furyl)-2-oxoethyl]-2-methyl-5-ethoxycarbonylpyrimid-6-oneYield 31%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

5-Ethoxycarbonyl-2-methylpyrimid-4-one (3.5 g, 19 mmol) was dissolved in DME (110 mL) and TBAF (28.5 mL, 1 M solution in THF, 28.5 mmol) added dropwise at 0° C. The resulting solution was stirred ten minutes and a solution of 3-bromoacetyl-2,5-dimethylfuran (4.3 g, 20 mmol) in DME (10 mL) was added dropwise. The reaction was stirred at room temperature overnight. The solution was then concentrated in vacuo and partitioned between EtOAc and saturated aqueous NH4Cl. The EtOAc layer was separated and concentrated. The product was purified using flash silica chromatography (EtOAc/hexane=2:8 to 8:2), with the o-alkylated side product eluting at 4:6, and the desired N-alkylated product eluting at 8:2. The N-alkylated product was dried as a yellow solid, isolated in 31% yield; MS: 319 (M+H) and 273.

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. concentrationThe solution was then concentrated in vacuo
  3. custompartitioned between EtOAc and saturated aqueous NH4Cl
  4. customThe EtOAc layer was separated
  5. concentrationconcentrated
  6. customThe product was purified
  7. washwith the o-alkylated side product eluting at 4:6
  8. washthe desired N-alkylated product eluting at 8:2
  9. customThe N-alkylated product was dried as a yellow solid
  10. customisolated in 31% yield

Sources & evidence

ORD record
ord-638ac5669feb4e09a9e5bbbde27df06b
Source dataset
uspto-grants-2002_02
Patent number
US06346534B1

Reaction notes

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