Electric Literature of 17564-64-6, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.
Electric Literature of 17564-64-6, In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 17564-64-6, name is 2-(Chloromethyl)isoindoline-1,3-dione belongs to indolines-derivatives compound, it is a common compound, a new synthetic route is introduced below.
LiHMDS (37 mL of a 1 M solution in THF, 37.0 mmol) was added dropwise to a stirred solution of benzyl 2-methyl-4-oxo-piperidine-1-carboxylate (7.5 g, 30.3 mmol) in THF (150 mL) at -78 C under N2. After 50 minutes, a solution of 2-(chloromethyl)isoindoline-1,3- dione (8.0 g, 40.9 mmol) in THF (30 mL) was added to the reaction mixture over 5 minutes. The solution was stirred for 2 hours then quenched with a saturated aqueous NH4Cl solution. After warming to ambient temperature, the reaction mixture was diluted with EtOAc, washed with saturated aqueous sodium bicarbonate solution and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, 0- 100% EtAOc/PE gradient elution) to give a mixture of benzyl 5-((1,3-dioxoisoindolin-2- yl)methyl)-2-methyl-4-oxopiperidine-1-carboxylate and benzyl 3-((1,3-dioxoisoindolin-2- yl)methyl)-2-methyl-4-oxopiperidine-1-carboxylate (2.4 g). This material was treated with DAST (8 mL, 61 mmol), with cooling in an ice bath. The resulting solution was stirred at 0 C for 15 minutes, then left to warm up to ambient temperature and stirred for 5 hours. The solution was poured carefully, dropwise, onto a stirred mixture of ice/water/NaHCO3/DCM. After 30 minutes, the organic phase was isolated and washed with brine. The organic was dried (Na2SO4), filtered and concentrated in vacuo. The crude mixture was purified by column chromatography (silica, 0- 100% EtOAc-PE gradient elution) give a colourless oil (1.5 g), of which 540 mg was dissolved in ethanol (15 mL) and hydrazine hydrate (100 muL, 2.0 mmol) added. The mixture was heated under relux for 3 hours then cooled to ambient temperature. The resulting suspension was filtered and the filtrate poured directly onto a pre-wetted ion-exchange cartridge. The cartridge was washed with methanol and the product eluted with a 2 M methanolic ammonia solution. The filtrate was concentrated under reduced pressure to give a pale yellow oil (300 mg). This material was dissolved in DCM (3 mL) and Et3N (200 muL, 1.4 mmol) was added under N2. The solution was cooled in an ice bath and methanesulfonyl chloride (100 muL, 1.3 mmol) added. After 5 minutes the cooling bath was removed and the mixture stirred at ambient temperature for 2 hours. The solution was diluted with DCM and saturated aqueous NaHCO3 solution. After stirring for 5 minutes, the organic phase was isolated using a phase separation cartridge. After concentration in vacuo, the residue was purified by column chromatography (silica, 0-100% [10% MeOH in EtOAc]-PE gradient elution) to give a pale yellow oil (150 mg). This material was taken up in DCM (3 mL) and Pd(OAc)2 (40 mg, 0.18 mmol), Et3SiH (150 muL, 0.94 mmol) and Et3N (100 muL, 0.72 mmol) were added. The reaction mixture was stirred at ambient temperature for 1 hour then diluted with MeOH. It was added onto a pre-wetted ion-exchange cartridge. The cartridge was washed with MeOH then the product eluted with a 2 M methanolic NH3 solution. The filtrate was concentrated under reduced pressure to give a brown oil (70 mg) containing a mixture of N-((4,4-difluoro-2- methylpiperidin-3-yl)methyl)methanesulfonamide A58 and N-((4,4-difluoro-6-methylpiperidin- 3-yl)methyl)methanesulfonamide A59, that was taken directly on to the next reaction; MS m/z: 234 (M+H)+.
In the field of chemistry, the synthetic routes of compounds are constantly being developed and updated. I will also mention this compound in other articles, 2-(Chloromethyl)isoindoline-1,3-dione, other downstream synthetic routes, hurry up and to see.
Reference:
Patent; MERCK PATENT GMBH; VERTEX PHARMACEUTICALS INCORPORATED; BAYLY, Andrew; BLEICH, Matthew; CHARRIER, Jean-Damien; DODD, James; DURRANT, Steven; ENO, Meredith Suzanne; ETXEBARRIA I JARDI, Gorka; EVERITT, Simon; FRAYSSE, Damien; KELLY, Shazia; KNEGTEL, Ronald; MOCHALKIN, Igor; MORTIMORE, Michael; NORTH, Kiri; PORICHIS, Filippos; PULLIN, Robert; RUTHERFORD, Alistair; STORCK, Pierre-Henri; TWIN, Heather Clare; XIAO, Yufang; (1159 pag.)WO2019/148132; (2019); A1;,
Indoline – Wikipedia,
Indoline | C8H9N – PubChem