N-Cyclohexyl-2,6-bis(1-methylethyl)-Benzenamine synthesis

Yield:1338363-23-7 66%

Reaction Conditions:

Stage #1: 2,6-diisopropylbenzenamine;cyclohexanonewith trimethylsilyl trifluoromethanesulfonate in N,N-dimethyl-formamide;Schlenk technique;Inert atmosphere;
Stage #2: with borane-THF in tetrahydrofuran;N,N-dimethyl-formamide at 0; for 3.83333 h;Schlenk technique;Inert atmosphere;

Steps:

General procedure B: Reductive amination of aryl amines and aldehydes/ketones with BH3·THF/TMSCl inDMF

General procedure: A dry 20 mL Schlenk tube with magnetic stirring bar was charged consecutively with300 μmol (1.0 eq) aryl amine, 330 μmol (1.1 eq) carbonyl substrate, 200 μL dry DMF and96.8 μL (750 μmol, 2.5 eq) TMSCl in a N2 counter-stream. The reaction mixture was cooledto 0 °C, the glass stopper was replaced by a rubber septum and 300 μL (300 μmol, 1.0 eq)BH3·THF (1.0 M solution in THF) were added slowly with a syringe over a period of 10 -20 min. The flask was sealed with a glass stopper and the reaction mixture was kept stirringat 0 °C until full conversion was detected by TLC. The vigorously stirred reaction mixture wascooled to 0 °C again and 3 mL H2O were added and the mixture was stirred for 20 min. 5 mLof EtOAc were added followed by 2.5 mL of a saturated Na2CO3 solution (CO2 evolution).The two phase mixture was kept stirring until the gas evolution had ceased (typically 20-60 min). In case the aqueous phase was turbid, small amounts of H2O were added to providea clear aqueous phase. The phases were separated and the aqueous layer was extractedwith EtOAc (5 x 8 mL). The combined organic layers were dried over Na2SO4, the dryingagent was removed by filtration and the solvents were removed using the rotary evaporator.The residue was dissolved in a small portion of EtOAc or MeOH and the 2.5-fold amount ofCelite (in respect to the mass of the crude product) was added. The solvents wereremoved in vacuum and the crude product (adsorbed onto Celite) was purified via silica gelchromatography.

References:

Pletz, Jakob;Berg, Bernhard;Breinbauer, Rolf [Synthesis,2016,vol. 48,# 9,p. 1301 - 1317] Location in patent:supporting information