Diisopropylethylamine → Tert-butyl 8-[(4-methoxyphenyl)methyl]-9-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl 4-hydroxy-4-[[(2-hydroxy-1-phenyl-ethyl)-[(4-methoxyphenyl)methyl]amino]methyl]piperidine-1-carboxylate (1.0 g, 2.13 mmol) in THF (10 mL) was added DIEA (1.1 mL, 6.38 mmol) followed by an addition of a solution of methylsulfonyl methanesulfonate (1.1 g, 6.38 mmol) in THF (2 mL) under an atmosphere of nitrogen at 0° C. The reaction mixture was warmed to room temperature and then heated at 40° C. for 16 hours. The reaction mixture was quenched with water and the aqueous layer was extracted with DCM. The organic layer was washed with a sat. solution of NaHCO3, followed by washing with water. The organic layer was dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0 to 100% DCM in hexanes as eluent to obtain tert-butyl 8-[(4-methoxyphenyl)methyl]-9-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (0.5 g, 51%). ESI-MS m/z calc. 452.6. found 453.5 (M+1)+; Retention time: 1.62 minutes (3 min run).

Provenance & Evidence