* 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.
6-(2,6-dichloro-4-nitrophenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
With caesium carbonate; In N,N-dimethyl-formamide; at 90℃; for 18h;Inert atmosphere;
In a 50 ml round-bottomed flask, <strong>[3107-19-5]1,3-dichloro-2-fluoro-5-nitrobenzene</strong> (467 mg, 2.22 mmol, Eq:1.00), tert-butyl2,6-diazaspiro[3.3]heptane-2-carboxylate (529 mg, 2.67 mmol, Eq: 1.2) andCs2C03 (1.81 g, 5.56 mmol, Eq: 2.5) were combined with DMF (10 ml) to give a yellow suspension. The mixture was heated to 90 oc and stirred under argon for 18 hours. TLCindicated total conversion. Cooled and the reaction mixture was diluted with H20 and EtOAc. The aqueous layer was washed with EtOAc (2 x 40 ml). The organic layers were combined, washed with H20 (2 x 25 mL), brine (1 x 25 mL), dried over Na2S04 and concentrated in vacuo to afford the desired product in quantitative yield as a bright yellow powder.MS -m/z: 386.9/389.0. (M-1)
With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; XPhos; In 1,4-dioxane; at 110℃; for 1h;Microwave irradiation; Inert atmosphere;
Preparation of intermediate N A solution of tert-butyl 2,6-diazaspiro[3.3]heptane-2-carboxylate (CAS [1041026-70- 3], 500 mg, 2.52 mmol), l-iodo-4-(trifiuoromethoxy)benzene (CAS [103962-05-6], 726 mg, 2.52 mmol), X-phos (240 mg, 0.504 mmol), Pd(dba)2 (145 mg, 0.252 mmol) and t-BuONa (969 mg, 10.1 mmol) in dioxane (8 mL) was irradiated under microwave at 110C for 1 hour under N2. Water was added to the mixture and the mixture was extracted with ethyl acetate (50 mL x 2). The organic layers were washed brine, dried over MgS04 and filtered. The filtrate was concentrated. The crude product was purified by column chromatography over silica gel (eluent: ethyl acetate/hexane from 0 to 1/5). The desired fractions were collected and concentrated to give N, 500 mg, 50%.
tert-butyl 6-(4-fluoro-2-(trifluoromethyl)benzoyl)-2,6-diazaspiro[3.3] heptane-2-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
51%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In tetrahydrofuran; at 20℃; for 16h;Inert atmosphere; Cooling with ice;
4-Fluoro-2-(trifluoromethyl)benzoic acid (1 equiv), amine (1 equiv) and DMAP (0.1 equiv) were added to THF (50mL) under nitrogen. The obtained solution was cooled down on an ice-water bath. EDC·HCl (1.3 equiv) was added to the solution, and the reaction mixture was stirred for 16h while warming at room temperature. The reaction solution was washed with water and extracted with EtOAc, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to yield pure product. 5.1.1.1 tert-Butyl 6-(4-fluoro-2-(trifluoromethyl)benzoyl)-2,6-diazaspiro[3.3] heptane-2- carboxylate (7a) (0022) White solid (yield 51%); MS (ESI+): [M+H]+: 389.2.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
