Reaction #70646

Reaction equation

benzylmagnesium chloride

THF

tert-butyl [1-(4-cyanophenyl)cyclobutyl]carbamate

THF

isopropylmagnesium chloride

THF

→

tert-butyl {1-[4-(phenylacetyl)phenyl]cyclobutyl}carbamate

Conditions

Workup

1. 1
   workup.STIRRINGto stir at −78° C. under an atmosphere of nitrogen for 10 minutes
2. 2
   OtherAfter 2 hours the reaction mixture was quenched at 0° C. by addition of a saturated solution of ammonium chloride
3. 3
   Temperatureto warm to room temperature
4. 4
   Washwashed with a saturated solution of ammonium chloride
5. 5
   Dryingdried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   OtherThe resulting residue was purified by silica gel chromatography (1-40% EtOAc/5% DCM/Hexane)

Procedure

A solution of tert-butyl [1-(4-cyanophenyl)cyclobutyl]carbamate (1-2) (16.6 g, 61.0 mmol) in anhydrous THF (300 mL) was cooled to −78° C. while stirring under an atmosphere of nitrogen. Then a 2.0 M solution isopropylmagnesium chloride in THF (30.5 mL, 61.0 mmol) was added dropwise over 5 minutes. The reaction mixture was permitted to stir at −78° C. under an atmosphere of nitrogen for 10 minutes. Then a 2.0 M solution of benzylmagnesium chloride in THF (116 mL, 232 mmol) was added dropwise over 10 minutes. The reaction mixture was permitted to warm to 0° C. After 2 hours the reaction mixture was quenched at 0° C. by addition of a saturated solution of ammonium chloride. The reaction was permitted to warm to room temperature, suspended in ethyl acetate, washed with a saturated solution of ammonium chloride, a saturated solution of sodium bicarbonate, followed by water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (1-40% EtOAc/5% DCM/Hexane) to give tert-butyl {1-[4-(phenylacetyl)phenyl]cyclobutyl}carbamate (1-3) as a waxy off-white solid. HRMS (M+Na)+: observed=388.1892, calculated=388.1883.

Source