Reaktion #1007922

Reaktionsgleichung

NH4Cl

MeI

2-(3,3-difluorocyclobutyl)acetonitrile

LDA

THF

→

Intermediate 226A

Ausbeute 41.0%

2-(3,3-Difluorocyclobutyl)-2-methylpropanenitrile

Ausbeute 41.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstir for 3 h
2. 2
   Extraktionthe compound was extracted with EtOAc (3×10 mL) The organic layer
3. 3
   Waschenwas washed with brine
4. 4
   Trocknendried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Sonstigethe filtrate evaporated in vacuo
7. 7
   SonstigeThe residue was purified by silica gel chromatography (12 g REDISEP® column, eluting with 30% EtOAc in petroleum ether)
8. 8
   workup.ADDITIONFractions containing the product
9. 9
   Sonstigeevaporated

Vorschrift

To a solution of 2-(3,3-difluorocyclobutyl)acetonitrile (300 mg, 2.288 mmol) in anhydrous THF (5 mL) was added a solution of LDA (6.86 mL, 6.86 mmol, 1 M in THF) dropwise at 0° C. and stirred at the same temperature for 1 h. MeI (0.715 mL, 11.44 mmol) was added dropwise at 0° C. and the reaction mixture was allowed to warm to RT and stir for 3 h. An aqueous saturated solution of NH4Cl was added and the compound was extracted with EtOAc (3×10 mL) The organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate evaporated in vacuo. The residue was purified by silica gel chromatography (12 g REDISEP® column, eluting with 30% EtOAc in petroleum ether). Fractions containing the product were combined and evaporated to afford the Intermediate 226A as a yellow oil (150 mg, 41%). 1H NMR (400 MHz, chloroform-d) δ ppm 2.42-2.76 (m, 4H), 2.14 (td, J=8.66, 3.26 Hz, 1H), 1.317 (s, 6H).

Quelle