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

Temperature

0 °C

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.

1. waitTo it, in small portions over approximately 90 minutes
2. customwas kept near 0° C. throughout this time
3. stirringThe reaction was stirred overnight under an atmosphere of N2
4. customgradually reaching room temperature
5. concentrationThe reaction was concentrated under vacuum
6. additionTo the residue was added approximately 50 mL water
7. extractionfrom this mixture was extracted the crude product with ethyl acetate (3×200 mL)
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated
10. customThe crude product was purified

ORD record

ord-7618d0ae5e3b44a7820cd2dadec9ffbc

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399489B2