tert-butyl 2-(4-aminophenoxy)ethylmethylcarbamate synthesis

Yield:1170071-27-8 95%

Reaction Conditions:

with hydrogen;palladium on activated charcoal in methanol at 50; for 1 h;

Steps:

82

Example 82Synthesis of te/*-butyl 2-(4-isocyanatophenoxy)ethyl(methyl)carbamate[00236] To a mixture 2-(methylamino) ethanol (5.0 g, 66.5 mmol) in 15ml of ethyl acetate was added a solution of (BoC)₂O (14.5 g, 66.5 mmol) in 5 mi of ethyl acetate dropwise with cooling in an ice bath The resulting mixture was stirred at room temperature for 2 hours, and the solvent was removed by evaporation under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, dried over Na^SO₄ and filtered. After removing the solvent, the crude tert-butyl 2-hydroxyethyl(methyl)carbamate was used without further purification for the next reaction (10.5 g, 90%) A solution of diisopropyl azodicarboxylate (5.22 g, 25.9 mmol) in 5 ml of THF was added dropwise to a solution of 4-nitryl phenol (3.0 g, 21 56 mmol), tert-butyl 2-hydroxyethyl(methyl)carbamate (4.53 g, 25.9 minol) and triphenylphosphine (6.78 g, 25.9 mtnol) in 60 ml of THF with ice-bath cooling under nitrogen atmosphere. The resulting mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure by evaporation. The residue was mixed with ether and filtered. The filtrate was concentrated and purified by flashing silica gel column (Petroleum ether/Ethyl acetate=10/l~8/l) to afford the intermediate /ert-butyl methyl(2-(4-nitrophenoxy)ethyl)carbamate (2.48 g. 39%) To a solution of this intermediate tert-butyl methyl(2-(4- nitrophenoxy)ethyl)carbamate (2.48 g, 8.4 mmol) in methanol was added Pd/C under hydrogen atmosphere. The mixture was heated to 50 ⁰C for 1 hour, and then cooled down to room temperature and filtered. The filtrate was concentrated to give the crude tert-butyl 2-(4-amuiophenoxy)ethyl(methyl)carbamate which was used without further purification for the next reaction (2.10 g, 95%). To a solution of t?phosgene (206 mg, 0.695 mmol) in DCM was added tert-butyl 2-(4-aminophenoxy)ethyl(methyl)carbamate (500 mg, 1.88 mmol) with ice-bath cooling followed by dropwise addition of TEA (380 mg, 3,76 mmol). After that, the mixture was stirred at room temperature for 2 hours. Tbe solvent was removed under reduced pressure without heating. The residue mixed with ether and filtered, The filtrate was concentrated to give tert-butyl 2-(4-isocyanatophenoxy)ethyl(methyI)carbamate (500 mg).

References:

WO2009/85562,2009,A1 Location in patent:Page/Page column 99-100