[CH2:1]1[C:3]2([CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:5]([C:16]([O:18][CH3:19])=[O:17])[CH2:4]2)[CH2:2]1.[Li+].[CH3:21]C([N-]C(C)C)C.C1COCC1.CCCCCCC.IC.[NH4+].[Cl-]>C1COCC1>[CH3:21][C:5]1([C:16]([O:18][CH3:19])=[O:17])[N:6]([C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[CH2:7][CH2:8][C:3]2([CH2:2][CH2:1]2)[CH2:4]16-tert-butyl 5-methyl 6-azaspiro[2.5]octane-5,6-dicarboxylate (D4) (420 mg, 1.56 mmol) was dissolved in THF (25 ml) and the solution was cooled at −78° C. prior addition of LDA 2M sol in THF/heptane (1.16 ml, 2.34 mmol). The red solution was left stirring at −78° C. for 40 min before adding iodomethane (0.146 ml, 2.34 mmol). The reaction was allowed to warm to RT and left stirring for 3 hrs. The resulting yellow-orange solution was treated with NH4Cl sat. sol. (5 ml) and extracted with Et2O (3×50 ml). Collected organic phases were washed with NaCl sat. sol. and dried over Na2SO4. Collected organics after solvent evaporation, afforded a residue which was purified by Biotage SNAP-Si (25 g) eluting with DCM. Collected fractions after solvent evaporation afforded the title compound (D5) (320 mg)
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