Ethyl Acetate → Ethyl 3-hydroxy-4,4-dimethoxypiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of potassium hydroxide (42 g, 752 mmol) in dry methanol (100 mL), at 0° C. and under an atmosphere of N2, was added a solution of ethyl 4-oxopiperidine-1-carboxylate (26.4 mL, 29.96 g, 175 mmol) in dry methanol (75 mL) via syringe. The resulting solution was stirred for an additional 30 minutes under an atmosphere of N2 at 0° C. To it, in small portions over approximately 90 minutes, was added iodobenzene diacetate (84.6 g, 262 mmol). Temperature was kept near 0° C. throughout this time. The reaction was stirred overnight under an atmosphere of N2, gradually reaching room temperature. Complete conversion was suggested by TLC (50% ethyl acetate in hexanes; Hanessian's stain; Rf˜0.25) in the morning. The reaction was concentrated under vacuum. To the residue was added approximately 50 mL water; from this mixture was extracted the crude product with ethyl acetate (3×200 mL). The organic layers were combined, dried over magnesium sulfate, and concentrated. The crude product was purified using column chromatography (silica gel; 10-65% ethyl acetate in hexanes), yielding 26.74 g (66%) of a pale yellow oil.

Provenance & Evidence