1-Pyrrolidinecarboxylic acid, 4-aMino-2-(difluoroMethyl)-, 1,1-d synthesis
- Product Name:1-Pyrrolidinecarboxylic acid, 4-aMino-2-(difluoroMethyl)-, 1,1-d
- CAS Number:1207852-96-7
- Molecular formula:C10H18F2N2O2
- Molecular Weight:236.26
1207852-95-6
1207852-96-7
Preparation of compound 25f: tert-butyl (2S,4α)-4-amino-2-(difluoromethyl)pyrrolidine-1-carboxylate 25e (1.5 g, 0.0057 mol) and triphenylphosphine (PPh3, 3.0 g, 0.0114 mol) were dissolved in a solvent mixture of tetrahydrofuran (THF, 50 mL) and water (5 mL), and stirred for 72 hours at room temperature. After completion of the reaction, the reaction mixture was concentrated under vacuum to give a residue. The residue was dissolved in ethyl acetate (EtOAc, 50 mL) and acidified by adjusting to pH~4 with 5% aqueous citric acid. The aqueous layer was separated and extracted with ethyl acetate (50 mL x 3). Subsequently, the aqueous layer was alkalized to pH~8 with solid sodium bicarbonate (NaHCO3), and then the alkalized aqueous layer was extracted with dichloromethane (50 mL × 3). The dichloromethane layers were combined, dried with anhydrous sodium sulfate (Na2SO4) and concentrated in vacuum to afford the target product (2S,4R)-4-amino-2-(difluoromethyl)-1-pyrrolidinecarboxylic acid-1,1-dimethylethyl ester 25f as a yellow oil (1.0 g, 76% yield).
![Ethanamine, N-[(3,5-dichlorophenyl)methylene]-2,2-diethoxy-](/CAS/20210305/GIF/1000210-73-0.gif)
1000210-73-0
0 suppliers
inquiry
1207852-96-7
18 suppliers
$459.23/5MG
Yield: 76%
Reaction Conditions:
with triphenylphosphine in tetrahydrofuran;water at 20; for 72 h;
Steps:
25
Preparation of compound 25f: tert-butyl (2S,4/?)-4-amino-2- (difluoromethyl)pyrrolidine-i -carboxylateA solution of 25e (1.5 g, 0.0057 mol) and PPh3 (3.0 g, 0.0114 mol) in THF (50 ml_) and water (5 ml_) was stirred at room temperature for 72 h. The reaction mixture was concentrated in vacuo to give residue, which was dissolved in EtOAc (50 ml_). The EtOAc layer was acidified with 5% aqueous citric acid to pH ~ 4. The separated aqueous layer was extracted with EtOAc (50 ml_χ3) and then basified with solid NaHCO3 to pH ~8, The basified aqueous layer was extracted with dichloromethane (50 ml_χ3). The combined dichloromethane layers were dried over Na2SO4 and concentrated in vacuo which gave the title compound 25f as yellow oil (1.0 g, 76%).
References:
PFIZER INC.;NINKOVIC, Sacha;BRAGANZA, John Frederick;COLLINS, Michael Raymond;KATH, John Charles;LI, Hui;RICHTER, Daniel Tyler WO2010/16005, 2010, A1 Location in patent:Page/Page column 120; 122