* 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 sodium hydride; In DMF (N,N-dimethyl-formamide); at 0 - 20℃;
A solution of 4-nitroindole (4.0 g, 24.7 mmol) in DMF (20 mL) was added slowly over 5 min to a suspension of unwashed sodium hydride (1.09 g, 60 wt.% in mineral oil, 27.2 mmol) in DMF (50 mL) at 0C. An immediate color change to deep red occurred with bubbling of escaping gasses. The reaction mixture was stirred at 0C for 5 min and then at RT for 40 min. A solution of Example 273 Part A(2) compound (12.6 g, 29.6 mmol) in DMF (20 mL) was added and the reaction mixture was stirred at RT over a weekend (64 h total). The solvent was removed under high vacuum on a rotary evaporator, and the resulting orange residue was partitioned between EtOAc (200 mL) and H2O (50 mL). The organic layer was washed with H2O (2 x 50 mL) and brine (50 mL), dried over MgSO4, and concentrated to give a yellow foam. The crude product was purified by flash chromatography on silica gel (600 g) eluting with a step gradient of 20% to 25% to 30% EtOAc/hexane to give title compound (10.9 g, 73%) as a yellow foam.
To a stirred solution of 4-nitroindole (4.0 g, 24.6 mmol) in CH2Cl2 (50 mL) were added catalytic amount of DMAP (Catalyst) and Boc2O (5.9 g, 27.1 mmol) at 0 C., and the resulting reaction mixture was stirred at room temperature for additional 3 h. The mixture was diluted with CH2Cl2, and washed with water. The organic phase was dried over MgSO4. The solvent was removed under reduced pressure to give 1-Boc-4-nitroindole as white solid (6.14 g, 95% yield). MS (ESI) m/z 262.1
95.8%
dmap; In toluene; at 20℃; for 1.75h;Product distribution / selectivity;
Step 1: Preparation of 4-Nitro-indole-1-carboxylic acid tert-butyl ester (2) To a 5 L four-necked round bottom flask equipped with mechanical stirrer, nitrogen inlet, thermocouple, and condenser was charged 182.3 g (1.124 mol) of 4-nitroindole, 1400 mL toluene, and 2.7 g of DMAP. At room temperature, solid BOC2O (270.0 g 1.237 mol, 1.10 eq) was added in portions over about 45 minutes to the stirring mixture while maintaining moderate gas evolution. After stirring the resulting solution for 1 hour, HPLC analysis showed the reaction to be complete with no starting material. The batch was quenched with 500 mL water, transferred to a separatory funnel and the phases were split. The organic layer was washed with 500 mL brine, concentrated to a slurry, diluted with 1000 ml heptane, filtered, and washed with fresh heptane. The filter cake was dried under vacuum at RT to constant weight to afford 206.0 gram of pale yellow solid. A second crop of 20.0 gram of product was isolated as post-precipitate from the mother liquors. The overall yield was 226.0 gram, 95.8% yield of pale yellow solid (100 area % HPLC).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
