Epibromohydrin → HCID 9813123, compound

Participants

Reaction Conditions

Reaction Steps

(4-Chlorophenyl)acetonitrile (1-1) (14.04 g) was dissolved in freshly distilled tetrahydrofuran (250 mL) and stirred at −78° C. under argon. Methyl lithium (LiBr complex, 1.5 M in diethyl ether, 62 mL, 1 eq) was added dropwise such that the reaction temperature stayed below −66° C. The solution was stirred for one h at −78° C. and turned from yellow to deep red. Epibromohydrin was added dropwise and the solution was stirred for an additional 90 min. Methylmagnesium iodide (3.0 M in diethyl ether, 31 mL) was added and the solution turned light brown as it was slowly warmed to room temperature and stirred overnight. The reaction was quenched with water (75 mL) and acidified to pH 2 with 5 N aqueous hydrochloric acid (ca. 30 mL). Brine was added until the layers separated. The organic layer was collected and the aqueous layer was reextracted with diethyl ether (2×50 mL). The organic layers were combined, dried with magnesium sulfate, filtered and concentrated to give crude 1-(4-chlorophenyl)-3-hydroxycyclobutane-1-carbonitrile (1-2).

Provenance & Evidence