Formaldehyde → Tert-butyl 4-(4-hydroxybut-2-yn-1-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 4-(3,3-dibromoprop-2-en-1-yl)piperidine-1-carboxylate from step 1 of this Example (19.5 g, 50.9 mmol) was dissolved in THF (170 mL) and cooled to −78° C. n-BuLi (2.5 Min hexanes, 46.8 mL, 117 mmol) was added slowly, maintaining internal temperature below −65° C. The mixture was stirred for additional 30 min, before paraformaldehyde (4.59 g, 152.7 mmol) was added in one portion. The reaction was stirred at −78° C. for 30 min and warmed to room temperature and allowed to stir at RT for 1 hour. Saturated aqueous ammonium chloride was added, and the aqueous layer was extracted 3 times with ethyl acetate. Column chromatography eluting with 30% acetone/hexanes afforded the product as colorless oil.

Provenance & Evidence