N,N-Dimethylformamide di-tert-butyl acetal

N,N-Dimethylformamide di-tert-butyl acetal may be used in the synthesis of following:

• (S)-2-(1-tert-butoxycarbonyl-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}ethylamino)benzoic acid methyl ester
• 3-O-tert-butylmorphine
• tert-butylesters of pyrrole- and indolecarboxylic acids

Reagent used for the preparation of indolizines via intermolecular cyclization of picolinium salts.

Synthetic Communications, 15, p. 723, 1985 DOI: 10.1080/00397918508063864

N,N-Dimethylformamide di-tert-butyl acetal is an derivatizing reagent.

reagent type: derivatization reagent
reaction type: Acylations

A mixture of 59.5 g (0.5 mol) of N, N-dimethylformamide dimethyl acetal and 147 mL (1.5 mol) of dry tert-butanol in a three-necked flask (250 mL) fitted with a thermometer magnetic stirrer, nitrogen inlet and a 33 x 1.9 cm silvered vacuum jacketed Goodloe column which was equipped with a reflux controlled take-off distilling head was heated at reflux for 1 hr, then 300 mg of 2,4,6-tri-tert-butylphenol was added. The reaction mixture was heated at 100-115°C for 48 hrs, during which time, at the rate of two drops/min, 56 mL of distillate was collected. Another 50 mL (0.52 mol) of tert-butanol was added to the reaction mixture, and the removal of methanol was continued for an additional 42 hrs to afford 64 mL of distillate. Distillation of the crude product with a similar but smaller column (20 x 1.4 cm) gave 53.2 g (52%) of N, N-Dimethylformamide di-tert-butyl acetal[1].

[1] Mohacsi, E. “A New Synthetic Method for the Preparation of N,N-Dimethylformamide DI-Tert-Butyl Acetal.” Synthetic Communications 15 1 (1985): 723–725.