Methyl iodide → 2-(3,3-Difluorocyclobutyl)-2-methylpropanenitrile

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).

1. stirringstir for 3 h
2. extractionthe compound was extracted with EtOAc (3×10 mL) The organic layer
3. washwas washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customthe filtrate evaporated in vacuo
7. customThe residue was purified by silica gel chromatography (12 g REDISEP® column, eluting with 30% EtOAc in petroleum ether)
8. additionFractions containing the product
9. customevaporated

ORDレコード

ord-7f9147541a7d4bbd9ae9d5dbff2e32bd

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09273058B2