p-Bromochlorobenzene → Tert-butyl 8-(4-chlorophenyl)-8-hydroxy-5-azaspiro[2.5]octane-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a flame-dried 100 mL three necked flask, a solution of 1-bromo-4-chlorobenzene (3.51 g, 18.36 mmol) in THF (20 mL) was cooled to −78° C. and treated with the dropwise addition of 1.6 M BuLi in hexanes (12.00 mL, 19.19 mmol) at a rate which did not allow the temperature to exceed −60° C. The mixture was stirred at −78° C. for 1 h, during which time a white precipitate was observed. The mixture was treated with the dropwise addition of a solution of tert-butyl 8-oxo-5-azaspiro[2.5]octane-5-carboxylate (1.88 g, 8.35 mmol) in THF (5 mL), at a rate which did not allow the temperature to exceed −60° C. The mixture was stirred for 3 h, then allowed to warm to −20° C. and quenched with saturated ammonium chloride solution. The mixture was extracted 3× with ethyl acetate, the combined organic phases were washed with water followed by brine, then dried over sodium sulfate and concentrated in-vacuo. The residue was purified over a 5×15 cm silica gel column, eluting with ethyl acetate/hexanes (5%-10%-15%-20% ethyl acetate, to yield the title compound (1.81 g, 5.36 mmol, 64.2% yield) as a colorless powder. MS (ESI+)=264.27, (M-tBuO)+, 220 (M−H2O-Boc)+.

Provenance & Evidence