Pyridine → HCID 18727980, compound

Participants

Reaction Steps

Dissolve N-(2-methoxyethyl)methylamine (5.81 g, 65.18 mmol) in 40 mL of pyridine at 0° C. and add acetic anhydride dropwise. After 30 minutes raise the reaction to room temperature and stir for 24 hours. Remove the solvent in vacuo and dissolve the residue in methylene chloride and wash with 5N HCl. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to give 4.23 g of crude N-(2-methoxyethyl)-N-methylacetamide. Dissolve this crude material (4.23 g, 32.25 mmol) in 50 mL of toluene and add Lawesson's reagent (6.5197 g, 16.12 mmol) to the mixture. Heat the reaction to 75° C. and allow it to stir for 18 hours. Remove the solvent in vacuo. Triturate the residue with a 1:1 mixture of diethyl ether/pentane three times decanting carefully from the residual solids. Combine the decanted layers and remove the solvent in vacuo to afford 2.13 g of crude N-(2-methoxyethyl)-N-methylthioacetamide. Dissolve this crude material (2.13 g, 14.47 mmol) in 50 mL diethyl ether and add methyl trifluoromethanesulfonate (2.49 g, 15.19 mmol) and allow the reaction to stir for 21 hours. Decant the diethyl ether from the oil and triturate the oil with diethyl ether (3×). Remove any excess diethylether from the oily residue in vacuo to obtain 2.92 g of crude triflic acid salt of (2-methoxyethyl)methyl(1-methylsulfanylethyl)amine as a black oil. Dissolve this black oil (2.92 g, 9.38 mmol) in 50 mL of pyridine and add (R)-(6-amino-2(R)-hydroxyindan-1-yl)carbamic acid tert-butyl ester (2.46 g, 9.31 mmol) and allow the reaction to stir at room temperature for 23 hours. Remove the solvent in vacuo and dissolve the residue in methylene chloride and wash with saturated aqueous sodium hydrogencarbonate. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo. Purify the residue by Biotage chromatography (10% MeOH/EtOAc to 25% MeOH/EtOAc) to afford 1.304 g of the titled product (37% yield). MS (ES): m/z 378.2 (M+H).

Provenance & Evidence