* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With 2,6-dimethylpyridine; In toluene; for 48h;Reflux;
A solution of 9.26 g (42.4 mmol) of <strong>[64628-73-5]3-chloro-4-trifluoromethoxy-phenylamine</strong> and 4.39 ml (42.4 mmol) of 2,6-lutidine in 50 ml of toluene was treated slowly with 7.30 ml (42.4 mmol) of tert-butyl 3-bromopropionate and stirred 2 days at reflux temperature. The reaction was then partitioned between aqueous 10% KHS04 and EtOAc (3x). The organic phases were washed with 10%> NaCl, dried over Na2S04 evaporated and purified by flash silica gel column (n -heptane :EtO Ac 9:1) to yield 9.59 g (60%>) of the title compound as brown liquid. MS: 339 (M+, CI).
60%
With 2,6-dimethylpyridine; In toluene; for 48h;Reflux;
A) 3-(3-Chloro-4-trifluoromethoxy-phenylamino)-propionic acid tert-butyl ester A solution of 9.26 g (42.4 mmol) of <strong>[64628-73-5]3-chloro-4-trifluoromethoxy-phenylamine</strong> and 4.39 ml (42.4 mmol) of 2,6-lutidine in 50 ml of toluene was treated slowly with 7.30 ml (42.4 mmol) of tert-butyl 3-bromopropionate and stirred 2 days at reflux temperature. The reaction was then partitioned between aqueous 10% KHSO4 and EtOAc (3*). The organic phases were washed with 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane:EtOAc 9:1) to yield 9.59 g (60%) of the title compound as brown liquid. MS: 339 (M+, Cl).
(+/-)-tert-butyl 4-(2-chloro-6-fluorophenyl)-4-cyanobutanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
41%
[0585] To a solution of (2-chloro-6-fluorophenyl)acetonitrile (2.00 g, 11.8 mmol) in THF (15 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (8.8 ml, 18 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, tert-butyl 3-bromopropanoate (2.2 ml, 14 mmol) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water was added gradually to the mixture, which was extracted twice with ethyl acetate. The combined organic phases were washed once with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated, and the residue was prepurified by flash column chromatography (50 g silica gel Biotage Snap-Cartridge KP-Sil, cyclohexane/ethyl acetate gradient 93:7→6:4, Isolera One). This was followed by repurification by preparative HPLC (Method 16). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 1.45 g (100% purity, 41% of theory) of the title compound. [0586] LC-MS (Method 1): Rt=2.16 min; MS (ESIpos): m/z=298 [M+H]+
(+/-)-tert-butyl 4-cyano-4-(2-fluorophenyl)butanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
4.22 g
[0604] To a solution of <strong>[326-62-5](2-fluorophenyl)acetonitrile</strong> (5.00 g, 37.0 mmol) in THF (35 ml) under argon was added gradually while stirring, at -78C., a 2 M solution of LDA in THF (22 ml, 44 mmol). The mixture was allowed to come to 0C. and, after 15 min, cooled back down again to -78C. Subsequently, a solution of tert-butyl 3-bromopropanoate (7.0 ml, 44 mmol) in THF (10 ml) was slowly added dropwise thereto at -78C. while stirring. Stirring of the mixture was continued overnight, in the course of which the cooling bath (dry ice/acetone) was allowed to come gradually to RT. Subsequently, water and ethyl acetate (100 ml of each) were gradually added at about 0C. to the mixture, which was agitated. After phase separation, the aqueous phase was extracted once with ethyl acetate (100 ml). The combined organic phases were washed once with saturated aqueous sodium chloride solution (150 ml), dried over sodium sulfate, filtered and concentrated, and the residue was taken up in dichloromethane and purified by flash column chromatography (100 g silica gel Biotage Snap-Cartridge Ultra, cyclohexane/ethyl acetate gradient 93:7?7:3, Isolera One). The combined target fractions were concentrated and the residue was dried under reduced pressure. This gave 4.22 g (69% purity, 29% of theory) of the title compound. [0605] LC-MS (Method 1): Rt=2.08 min; MS (ESIpos): m/z=264 [M+H]+
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
