3-HYDROXY-PROPIONAMIDINE HCL synthesis

Yield:53868-56-7 100%

Reaction Conditions:

Stage #1: 3-Hydroxypropionitrilewith acetyl chloride in methanol;toluene at 0 - 20; for 18 h;
Stage #2: with ammonia in methanol at 0 - 20; for 18 h;

Steps:

Intermediate I-54A: 3-hydroxypropanimidamide, HCl

To a mixture of MeOH (5 mL, 124 mmol)/toluene (30.1 mL) at 0 °C was added acetyl chloride (3.00 mL, 42.2 mmol) slowly over 10 minutes. The reaction mixture was allowed to stir at 0 °C for 10 minutes then at room temperature for 10 minutes. Thereaction mixture was cooled to 0 °C and 3-hydroxypropanenitrile (1.5 g, 21.10 mmol) dissolved in 5 mL of toluene added and the reaction mixture was allowed to stir at room temperature for 18 h. The reaction mixture was cooled to 0 °C and 7N ammonia in MeOH (15.07 mL, 106 mmol) was added carefully over 5 minutes. The reaction mixture was then allowed to warm to room temperature and stirred for 18 h at room temperature.The mixture was then filtered through celite and the filter cake washed with 2:1 toluene/MeOH. The filtrate was concentrated to yield Intermediate I-54A in quantitative yield. The product was brought forward without further purification. ‘H NMR (400MHz, DMSO-d6) ? 3.70 (t, J=5.9 Hz, 2H), 2.77 (t, J5.9 Hz, 2H).

References:

WO2018/13776,2018,A1 Location in patent:Page/Page column 150; 151