Ethyl diacetoacetate 12.50g (72.6 mmol) was added to a stirred slurry of caesium carbonate 50.5g (155mmol) in anhydrous acetonitrile (300mL) in a 1L flask. A white voluminous precipitate formed. The mixture was stirred for 30 min at RT, then cooled to 0C. Neat methyl triflate 9.5mL (86mmol, DANGER) was carefully added, dropwise over 10 min and the mixture was stirred under Ar on a melting ice bath (0 to 20C) for 1 hour, then at ambient temperature for 11 hours (overnight). The entire slurry was concentrated to a small volume on rotavap. Solid formamidinium acetate 31.2g (300mmol) was added to the residue followed by a solution of sodium ethoxide, made freshly by dissolving sodium metal 5.05g (220 mmol) in 0.5L of anhydrous non-denatured ethanol. The mixture was refluxed on oil bath under blanket of Ar for 4 hours. (Some ammonium carbonate sublimate deposited in the reflux condenser). The reaction mixture was cooled, filtered and the filtrates evaporated. The residue was portioned between dichloromethane 0.4L and sat. bicarbonate solution 0.5L with some additional water (100mL). The aqueous phase was re-extracted three times with dichloromethane (3x250mL). The combined organic extracts were filtered to break the emulsion, washed with sat. bicarbonate 0.5L, dried (MgSO4) and evaporated. The residue was purified on a column of silica 250g in hexane-EtOAc 3:2 mixture. The purified product (7.5g of a pale-yellow oil) was re-distilled at reduced pressure , b.p. 105-110C/20 Torr. Y=6.307g (48%) of a colorless liquid.
1H(CD3CN, 400MHz): 8.902(s, 1H), 4.409(q, 7.1Hz, 2H), 2.482(s, 6H), 1.364(t, 7.1Hz, 3H)
Note: On cannot be careful enough when working with methyl triflate. The vapor inhalation can cause lethal lung edema, skin absorption will cause painful blisters and the long-term effect is genotoxicity and cancer. Be careful when opening the MeOTf ampule, work with the stuff only in the hood. Evaporating some concentrated ammonia can be used to decontaminate the rotavap after the methylation step. Leave the MeOTf syringe to dry up in the back of the hood. Use double gloves. Do not try to clean a MeOTf spill – evacuate.