Some common heterocyclic compound, 6276-54-6, name is 3-Chloropropan-1-amine hydrochloride, molecular formula is C3H9Cl2N, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route. category: chlorides-buliding-blocks
Triethylamine (51.0 g) was added dropwise to a solution of di-tert-butyl dicarbonate (100.0 g) and 3-chloropropylamine hydrochloride (71.5 g) in methanol (400 mL) at 0 C., and the mixture was then stirred at the same temperature for 16 hours. Thereafter, toluene (400 mL) and water (400 mL) were added to the reaction solution for liquid separation, and the organic layer was then washed with water. 400 mL of toluene was added to the organic layer, and the mixed solution was concentrated to 300 mL under reduced pressure. After that, N,N-dimethylacetamide (210 mL) was added, and the mixed solution was concentrated to 300 mL under reduced pressure. Thereafter, to this solution, potassium carbonate (126.66 g), tetrabutylammonium bromide (44.32 g), dimethyl malonate (90.82 g) and N,N-dimethylacetamide (100 mL) were added, and the mixed solution was then stirred at 55 C. for 20 hours. Thereafter, toluene (400 mL) and water (700 mL) were added to the reaction solution for liquid separation. The organic layer was successively washed with water, a 1 M aqueous sodium hydroxide solution and water, and was then concentrated to 150 mL under reduced pressure. To this solution, methanol (1870 mL) and a 1 M aqueous sodium hydroxide solution (430.8 mL) were added, and the mixed solution was then stirred at 0 C. for 27.5 hours. Subsequently, concentrated hydrochloric acid (2.5 mL) was added to the reaction solution, so that the pH of the solution was adjusted to pH 7-9, and the solution was then concentrated to 375 mL under reduced pressure. Ethyl acetate (500 mL) was added to the reaction solution, and concentrated hydrochloric acid (35.1 mL) was then added to the mixed solution, so that the pH of the solution was adjusted to pH 2.2-2.5, followed by liquid separation. The water layer was extracted with ethyl acetate (500 mL), the organic layer was then mixed therewith. The mixed solution was dehydrated and concentrated under reduced pressure to prepare an ethyl acetate (250 mL) solution. To the obtained solution, ethyl acetate (500 mL) and morpholine (37.5 g) were added, and the obtained mixture was stirred overnight. Thereafter, the precipitated crystals were filtrated, were then washed with ethyl acetate, and were then dried under reduced pressure to obtain the title compound (136.1 g, yield: 81.9%). (0118) 1H-NMR (DMSO-d6) delta: 6.79 (1H, t, J=5.5 Hz), 3.61 (4H, t, J=4.9 Hz), 3.58 (3H, s), 3.14 (1H, t, J=7.8 Hz), 2.90-2.80 (6H, m), 1.74-1.59 (2H, m), 1.37 (9H, s), 1.34-1.25 (2H, m) .
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 6276-54-6, its application will become more common.
Reference:
Patent; DAIICHI SANKYO COMPANY, LIMITED; HAYASHI, Masaki; UKAI, Kazutoshi; (16 pag.)US2018/29993; (2018); A1;,
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