Epibromohydrin → HCID 9813123, compound

Temperature

-78 °C

(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).

1. customstayed below −66° C
2. stirringThe solution was stirred for one h at −78° C.
3. stirringthe solution was stirred for an additional 90 min
4. temperaturewas slowly warmed to room temperature
5. stirringstirred overnight
6. customThe reaction was quenched with water (75 mL)
7. additionBrine was added until the layers
8. customseparated
9. customThe organic layer was collected
10. dry with materialdried with magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated

ORD record

ord-9b52d1855ac44cb9a5f1246e1d0457d4

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07875642B2