Formamides amines, tert

Formamides from tert. amines—Oxidative opening of N-heterocycles s. 13, 228 s. a. Soc. 1960, 3559... 

Chromium trioxide I pyridine Formamides from tert. amines... 

Preparation ofS [1] A solution of N-(tert-butyloxy)carbonyliminodiacetic acid (1) (0.349 g, 1.50 mmol) in dimethyl formamide (DMF) (15 ml) was treated with N -(3-dimefhylaminopropyl)-N-ethyl-carbodiimide hydrochloride (EDC) (0.294 g, 1.54 mmol) at 25 °C. The mixture was stirred at 25 °C for 1 h, and then the amine (1 equiv.) was added and the reaction mixture was stirred for 20 h. It was then poured into 10% aqueous HCl (60 mL) and extracted with ethyl acetate (100 mL). The organic phase was washed with 10% HCl (40 mL) and saturated aqueous NaCl (2 x 50 mL), dried (NazSOr), filtered, and concentrated in vacuo to yield the diacid monoamides 2. Each of the diacid monoamides 2 was dissolved in anhydrous DMF (20 mL/mmol) and the solutions obtained were divided into three equal portions in three separate vials. Each solution was then treated with one of the three amines (1 equiv.), diisopropylefhylamine (2 equiv.), and (benzotriazol-l-yloxy)tripyr-rolidinophosphonium hexafluorophosphate (PyBOP) (1 equiv.). Each solution was stirred at 25 °C for 20 h. The respective mixture was then poured into 10% HCl and extracted with ethyl acetate. The organic phase was washed sequentially with 10% HCl, saturated aqueous NaCl, 5% aqueous NaHCOs, and further saturated aqueous NaCl, then dried (Na2SO4), filtered, and concentrated to yield the diamides 3. Each of the diamides 3 was dissolved in 4 N HCl/dioxane (32 mL/mmol) and the respective mixture was stirred at 25 °C for 45 min. The solvent was then removed in vacuo, the residue was dissolved in anhydrous DMF (28 mL/mmol), and the solution obtained was divided into three equal portions, which were placed in three separate vials. Each solution was treated with one of three carboxylic acids (1 equiv.) followed by diisopropylamine (3 equiv.) and PyBOP (1 equiv.) and the mixtures were stirred for 20 h. Each mixture was then poured into 10% HCl and extracted with ethyl acetate. The organic phase was washed sequentially with 10% HCl, saturated aqueous NaCl, 5% aqueous NaHCOs, and further saturated aqueous NaCl, then dried (Na2SO4), filtered, and concentrated in vacuo to yield the final products 5. 

S. (S)-N,II-Dimethyl-S -(l-tez t-butoxy-3-methyl-2-butyl)formamldine (2). In a 500-mL, round-bottomed flask 26 g (140 mmol) of the formamide from Part A is dissolved in 100 ml of ethanol and 200 mL of a 50% aqueous potassium hydroxide solution is added. The mixture is heated at reflux overnight upon cooling, the reaction separates into colorless aqueous and organic layers. The two layers are extracted three times with 100 mL of ether and the combined organic layers are washed with 100 mL of brine. After the solution is dried over anhydrous potassium carbonate and filtered, the ether and ethanol are carefully removed under aspirator vacuum at ambient temperature. The crude amine is treated with 25 g (210 mmol) of N,N-dimethylformamide dimethyl acetal (Note 8) and the reaction mixture is heated under argon at 40°C for 1 hr. The solution is concentrated under reduced pressure and the crude product is distilled bulb-to-bulb (0.05 mm, 55-65°C) to give 25.7-27 g (86-91.5%) of (S)-N,N-dimethyl-N -(l-tert-butoxy-3-methyl-2-butyl)formamidine (2) as a colorless liquid (Note 9). 

---