Cyclobutanecarboxylicacid,1-amino-,methylester,hydrochloride(9CI)

To a stirred solution of 1-aminocyclobutane-l-carboxylic acid (2.7 g, 23.4 mmol) in MeOH (40 ml), was carefully added acetyl chloride (4.2 ml, 58.6 mmol) drop wise at 0 °C. The reaction mixture was then warmed to room temperature and stirred for about 12 hours. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure to give methyl 1-aminocyclobutane-l -carboxylate hydrochloride (3.02 g, yield: 100 percent) as a white solid.To a stirred solution of methyl 1-aminocyclobutane-l -carboxylate hydrochloride (3.02 g, 23.4 mmol) in THF (40 ml), were added N(Et)1-Aminocyclobutamic acid (250 mg, 2.17 mmol) was dissolved in 10 mL of anhydrous methanol, 0.3 mL of thionyl chloride was added dropwise to the ice bath, Remove the ice bath and heat the reflux overnight.Evaporated to dryness under reduced pressure to give 1-aminocyclopropylcarboxylic acid hydrochloride (280 mg) as a white solid in 78percent yield.1-aminocyclobutanecarboxylic acid (100 mg) was dissolved in 10 ml of methanol, and the reaction solution was cooled to 0°C.At 0-5°C, HCl gas was introduced and stopped after 2 hours. The reaction solution was warmed to room temperature and reacted at room temperature for 18 hours. The mixture was concentrated under reduced pressure to give a yellow oil.Add 15 ml of ether to the concentrate and stir for 30 minutes.Filtered to give 10 mg (71percent yield) of the title compound as a white solid.1-aminocyclobutanecarboxylic acid hydrochloride (5.2 g, 34.5 mmol) and methanol (120 ml) were charged. An ice bath was set, and thionyl chloride (3.7 ml, 51.7 mmol) was slowly added thereto. Then, the ice bath was removed, and the mixture was stirred at room temperature for 3 hours. The resultant product was vacuum-distilled to remove a solvent, and dried in a 60 oven so as to obtain methyl-1-aminocyclobutanecarboxylate hydrochloride (5.62 g, 37.1 mmol, 98 percent).[677] Example 6 Under a nitrogen atmosphere, 3.0 g (20.0 mmol, 1.0 eq) of To a 100 mL reactor was added 3.0 g (18 mmol, 1.0 eq) of