Imidazole → 4-Chloro-α-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]benzeneacetonitrile

TBS-Cl (2.29 g, 15.2 mmol) in dry DMF (12 mL) was added to a solution of 2-(4-chlorophenyl)-3-hydroxypropanenitrile (2.30 g, 12.7 mmol) and imidazole (3.45 g, 50.7 mmol) in DMF (20 mL) at 0° C. under nitrogen. The reaction mixture was warmed to room temperature and stirred overnight. The reaction mixture was partitioned between ether and water. The organic layer was washed with brine, dried and concentrated. The residue was purified by column (hexanes:EtOAc, 30:1) to give 3-(tert-butyldimethylsilyloxy)-2-(4-chlorophenyl)propanenitrile (3.40 g, 91%) as a colorless oil. A solution of EtMgBr in THF (3.0 M, 7.0 mL, 21 mmol) was added dropwise at room temperature to a stirred solution of this 3-(tert-butyldimethylsilyloxy)-2-(4-chlorophenyl)propanenitrile (3.1 g, 10 mmol) and Ti(i-PrO)4 (3.4 mL, 11 mmol) in Et2O (60 mL). After the mixture was stirred at room temperature for 1 hour, BF3OEt (2.7 mL, 21 mmol) was added at once. The mixture was stirred for an additional 1 hour. A solution of 10% NaOH (10 mL) was added, followed by DCM (300 mL). The resulting precipitate was filtered and washed with DCM. The combined filtrates were dried and concentrated. The residue was purified by column chromatography (30:1 DCM:MeOH) to give 1-(2-(tert-butyldimethylsilyloxy)-1-(4-chlorophenyl)ethyl)cyclopropanamine (2.3 g, 67%) as a colorless oil. LCMS: 326.1 [M+H+] (APCI+); Rf: 3.04 min.

1. customThe reaction mixture was partitioned between ether and water
2. washThe organic layer was washed with brine
3. customdried
4. concentrationconcentrated
5. customThe residue was purified by column (hexanes:EtOAc, 30:1)

ORD record

ord-c55ec0d0aed344f484e1daf8554bdba2

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303040B2