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
4
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.