Acetonitrile → 4-chloro-5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

HRID 529143Notes

Reaction equation

HRID 529143 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH2:6]([CH:8]1[C:16]2[C:15](O)=[N:14][CH:13]=[N:12][C:11]=2[CH2:10][CH2:9]1)[CH3:7].C(#N)C>>[Cl:3][C:15]1[C:16]2[CH:8]([CH2:6][CH3:7])[CH2:9][CH2:10][C:11]=2[N:12]=[CH:13][N:14]=1

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 24813Phosphorus oxychlorideHCID 178435582HCID 178435582, compound

Product 1

HCID 866518114-chloro-5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidineYield 26.6%

Conditions

Temperature
80 °C

Procedure

Phosphorous oxychloride (1.92 mL, 20.6 mmol) was added to a solution of 5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (1.13 g, 6.88 mmol) in acetonitrile (40 mL, 766 mmol) and heated to 80° C. The reaction was stirred at 80° C. for 15 hours. LCMS confirmed consumption of the starting material peak and conversion to a new product peak. The reaction was cooled to room temperature and concentrated under vacuum. The residue was partitioned between DCM and saturated aqueous NaHCO3. The organic layer was dried over anhydrous Na2SO4. The crude solution was concentrated under vacuum to an oil. The crude was purified by silica gel chromatography (gradient: 10-50% EtOAc/Hexanes). Purification provided 4-chloro-5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (334 mg, 1.83 mmol, 26.6% yield) as an oil. MS (APCI+) [M+H]: 183.0.

Workup

  1. customconsumption of the starting material peak and conversion to a new product peak
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated under vacuum
  4. customThe residue was partitioned between DCM and saturated aqueous NaHCO3
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationThe crude solution was concentrated under vacuum to an oil
  7. customThe crude was purified by silica gel chromatography (gradient: 10-50% EtOAc/Hexanes)
  8. customPurification

Sources & evidence

ORD record
ord-6d520aacf158402d9e12379e51ab8ef6
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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