Triethylamine → 2-Cyclobutyl-4-(dimethoxymethyl)pyrimidine

HRID 931110Notes

Reaction equation

HRID 931110 reaction equation
CN(C)[CH:3]=[CH:4][C:5](=O)[CH:6]([O:9][CH3:10])[O:7][CH3:8].Cl.[CH:14]1([C:18](=[NH:20])[NH2:19])[CH2:17][CH2:16][CH2:15]1.C(N(CC)CC)C>C(O)C>[CH:14]1([C:18]2[N:19]=[C:5]([CH:6]([O:9][CH3:10])[O:7][CH3:8])[CH:4]=[CH:3][N:20]=2)[CH2:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 27821454-(Dimethylamino)-1,1-dimethoxybut-3-en-2-oneHCID 20542589Cyclobutanecarboximidamide hydrochloride

Product 1

HCID 898540422-Cyclobutyl-4-(dimethoxymethyl)pyrimidineYield 12.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-(dimethylamino)-1,1-dimethoxybut-3-en-2-one (2.0 g, 11.5 mmol) in ethanol was added cyclobutanecarboximidamide hydrochloride (3.0 g, 22.3 mmol) and triethylamine (2.33 g, 23.0 mmol) under nitrogen at room temperature. The reaction mixture was refluxed for 16 h. The solvent was removed under reduced pressure. To the residue was added water and the mixture was extracted with ethyl acetate. The combined organics were dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified via column chromatography to afford 2-cyclobutyl-4-(dimethoxymethyl)pyrimidine as a colorless liquid (300 mg, 12%). MS (ES+APCI) (M+H) 209.2; LCMS retention time: 3.257 minutes (Method J).

Workup

  1. temperatureThe reaction mixture was refluxed for 16 h
  2. customThe solvent was removed under reduced pressure
  3. additionTo the residue was added water
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe combined organics were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified via column chromatography

Sources & evidence

ORD record
ord-b78243e5985c4b34b911760a8441cc87
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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