[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([Cl:9])[N:3]=1.Cl.[CH:11]12[O:18][CH:15]([CH2:16][CH2:17]1)[CH2:14][NH:13][CH2:12]2.CCN(CC)CC>CCO>[Cl:1][C:2]1[N:3]=[C:4]([N:13]2[CH2:12][CH:11]3[O:18][CH:15]([CH2:16][CH2:17]3)[CH2:14]2)[CH:5]=[C:6]([Cl:8])[N:7]=1.[Cl:9][C:4]1[CH:5]=[C:6]([Cl:8])[N:7]=[C:2]([N:13]2[CH2:12][CH:11]3[O:18][CH:15]([CH2:16][CH2:17]3)[CH2:14]2)[N:3]=12,4,6-Trichloropyrimidine (8, 6.325 mL, 55 mmol) was dissolved in 220 mL EtOH at 0° C. 8-Oxa-3-aza-bicyclo[3.2.1]octane hydrochloride (2, 8.23 g, 55 mmol) was added followed by the addition of NEt3 (23.1 mL, 165 mmol). The mixture was allowed to warm to room temperature and stirred for 1 hour at ambient temperature. The mixture was concentrated, dissolved in EtOAc and washed with saturated NaHCO3. The aqueous phase was extracted with EtOAc the combined organic phases were dried (MgSO4), filtered, and concentrated. The mixture was purified by silica gel chromatography (10-80% EtOAc in hexanes) to give 11.807 g (45 mmol, 83%) of 3-(2,6-dichloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (9) along with 1.631 g (6.2 mmol, 11%) of 3-(4,6-dichloro-pyrimidin-2-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (10).
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