Acetonitrile → 4-chloro-5-ethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine
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]=1Participants
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
- customconsumption of the starting material peak and conversion to a new product peak
- temperatureThe reaction was cooled to room temperature
- concentrationconcentrated under vacuum
- customThe residue was partitioned between DCM and saturated aqueous NaHCO3
- dry with materialThe organic layer was dried over anhydrous Na2SO4
- concentrationThe crude solution was concentrated under vacuum to an oil
- customThe crude was purified by silica gel chromatography (gradient: 10-50% EtOAc/Hexanes)
- customPurification
Sources & evidence
- ORD record
- ord-ec586296420e4aafa0be988dc33a670e
- Source dataset
- uspto-grants-2012_12
- Patent number
- US08324221B2
Reaction notes
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