Triethylamine → 2-Cyclopropylpyrimidine-4-carbonitrile

HRID 931260Notes

Reaction equation

HRID 931260 reaction equation
[CH:1]1([C:4]2[N:9]=[C:8]([CH:10]=O)[CH:7]=[CH:6][N:5]=2)[CH2:3][CH2:2]1.Cl.NO.C([N:17](CC)CC)C.CCCP(=O)=O>CN(C)C=O.O>[CH:1]1([C:4]2[N:9]=[C:8]([C:10]#[N:17])[CH:7]=[CH:6][N:5]=2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 16167369Propylphosphoric anhydrideHCID 299398122-Cyclopropylpyrimidine-4-carbaldehyde

Product 1

HCID 898530762-Cyclopropylpyrimidine-4-carbonitrileYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2-cyclopropylpyrimidine-4-carbaldehyde (1.0 g, 6.68 mmol) in N,N-dimethylformamide (10 mL) were added hydroxylamine hydrochloride (500 mg, 7.02 mmol) and triethylamine (1.2 mL). The reaction mixture was heated to 50° C. and propylphosphonic anhydride (T3P) was added dropwise. After 16 h at 110° C., the mixture was cooled to room temperature, diluted with water and quenched with solid sodium bicarbonate. The mixture was extracted with ethyl acetate, then the organic layer was dried over sodium sulfate, filtered, concentrated under reduced pressure. The residue was purified via silica gel chromatography to afford 2-cyclopropylpyrimidine-4-carbonitrile (600 mg, 62%) as a pale yellow liquid. MS (ES+APCI) (M+H) 145.9; LMCS retention time 2.224 min (Method G).

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. customquenched with solid sodium bicarbonate
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified via silica gel chromatography

Sources & evidence

ORD record
ord-c17d46817fa241b5a9946d14838037ad
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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