Cl.[C:2]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([OH:14])=O)[CH:7]=1)([CH3:5])([CH3:4])[CH3:3].C[N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C1COCC1.N1CCOCC1>ClCCl>[C:2]([C:6]1[CH:11]=[CH:10][N:9]=[C:8]([C:12]([N:16]2[CH2:21][CH2:20][O:19][CH2:18][CH2:17]2)=[O:14])[CH:7]=1)([CH3:3])([CH3:4])[CH3:5]Suspend 4-tert-butyl-pyridine-2-carboxylic acid hydrochloride (11.14 g, 51.8 mmol) in 50 mL dichloromethane, add 4-methylmorpholine (10.48 g, 11.4 mL, 104 mmol), stir, add 100 mL THF and stir the suspension a few minutes. Add N,N′-carbonyldiimidazole (8.4 g, 51.8 mmol) to the stirring suspension, note moderate gas evolution and stir the light suspension at room temperature for 30 to 90 minutes. Add morpholine (13.54 g, 13.61 mL, 155 mmol) via pipet, stir overnight at room temperature. Dilute the suspension with 400 mL dichloromethane, wash with 400 mL saturated aqueous sodium bicarbonate solution and back-extract the aqueous phase with 100 mL dichloromethane. Combine organic layers and wash with 300 mL portions of saturated sodium bicarbonate (once) and dilute aqueous saturated sodium chloride (three times). Dry the organic layers over MgSO4 concentrate to an oil and purify on a 400 g silica cartridge with a gradient of 0→10% acetone in EtOAc over 20 minutes. Pool, concentrate, and dry fractions to provide 10.24 grams of a viscous colorless oil. LCMS (ES) m/z 249 (M+1).
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