The 5-hydroxymethyl-4-methyl-3-morpholinone 11.53g (79.43mmol), DMAP 61mg (0.5mmol) and triethylamine 11.6mL (83.4mmol) was dissolved in anhydrous chloroform (200mL) and cooled to 0C. Mesyl chloride 6.45 mL (83.4mmol) was added dropwise over 5 min period. The mixture was stirred at 0C for 90 min, then quenched by addition of water 20mL. The quenched mixture was stirred at RT for 10 min, acidified with 1M sulfuric acid (40mL) and separated. The aqueous phase was re-extracted with chloroform (3x100mL). The combined extracts were dried (MgSO4) and filtered. The filtrates were applied directly onto a column of silica (200g) packed in chloroform. The column was eluted with 20:1 chloroform-methanol mixture. The purified product was carefully dried on highvac to remove traces of chloroform. Y=16.86g (95%) of pure mesylate as a colorless honey. (Using identical procedure, the opposite enantiomer was obtained in 94%Y, 16.63g)
1H(CDCl3, 400MHz): 4.378(m, 2H), 4.229(dAB, 16.4Hz, 1H), 4.133(dAB, 16.8Hz, 1H), 3.828(dd, 12.5Hz, 2.7Hz, 1H), 3.561(m, 1H), 3.086(s, 3H), 3.066(s, 3H); 13C(CDCl3, 100MHz): 166.92, 68.14, 65.87, 64.12, 56.87, 37.76(br s), 33.79(br s)
N,N,N’,N’,-Tetramethylguanidinium azide 7.91g (50mmol) solid (hygroscopic!) was added in one portion to a solution of the mesylate 6.85g (30.68mmol) in anhydrous acetonitrile 20mL and the mixture was stirred under nitrogen at 70C for 1 day. The cooled mixture was quenched by addition of saturated aqueous ammonium chloride 80mL and extracted with ethyl acetate (3x200mL). The combined organic extracts were dried (MgSO4) and evaporated, then re-evaporated with anh THF. The obtained crude azide (4.79g) was dissolved in anh THF 250mL, the solution was cooled to 0C and LAH 5.0g was gradualy added (in 1g portions) with vigorous stirring and cooling on ice bath. The mixture was then refluxed under nitrogen for 6 hours. The reaction mixture was cooled to 0C, quenched by carefull dropwise addition of water 5mL, then 15%NaOH 15mL and then water again 5mL. The quenched mixture was stirred at RT overnight (12 hours), the salts were removed by filtration (and washed with THF), the filtrates were concentrated. The obtained residue was distilled on Kugelrohr apparatus at 0.5Torr, air bath temperature 80-85C. Y=3.554g (89%) of a colorless liquid
1H(CD3CN, 400MHz): 3.750(m, 1H), 3.694(m, 1H), 3.502(td, t:11.3Hz,d:2.7Hz, 1H), 3.369(dd, 11.3Hz, 10.1Hz, 1H), 2.695(d, 2.7Hz, 1H), 2.684(d, 0.8Hz, 1H), 2.635(dt, d:9.4Hz, t:2.3Hz, 1H), 2.338(s, 3H), 2.229(m, 1H), 1.946(m, 1H), 1.531(br s, 2H); 13C(CDCl3, 100MHz): 70.70, 68.01, 65.75, 56.83, 43.56, 41.68
(A procedure for preparation of tetramethylguanidinium azide was posted on Sept 25).