Leucine methyl ester hydrochloride

Crystalline

Under ice bath, 100 ml round-bottom flask was added with 60 ml of methanol, and then slowly added with 4 ml of SOClTake 115mL methanol, added to 250mL three-necked flask, Cool to -13 ° C in a low temperature stirred reaction bath (Reaction should ensure that the environment is anhydrous, In the three-necked flask branch pipe connected to the drying tube; The reaction generates HCl and SO2 gases, To use lye absorption device), Then 9.5 mL (0.131 mol) of freshly distilled SOCl2 was slowly added dropwise, When dropping the reaction temperature is controlled below -10° C , To be added dropwise after completion, continue to react at -10° C 2h, rise to room temperature, 15.4 g (0.118 mol) of leucine was added, and the temperature was raised to 50 ° C. for 3 hours, followed by TLC (With methanol and methylene chloride 1: 1 mixture as a developer, To prevent tailing, drop a drop of diethylamine per ml) Until the end of the reaction (about 3h) Stop the reaction. After the solvent was distilled off by rotary evaporation, A large amount of white solid appears. The product was purified by recrystallization from methanol to give pure leucine methyl ester hydrochloride in 96percent yield.General procedure: A suspension of L-amino acid (50mmol) in methanol (50mL) was stirred under ice cold conditions. Thionyl chloride (5mL) was slowly dropped to the solution at−5°C. Then, the mixture was allowed to slowly warm to room temperature while being stirred. The reaction was monitored by TLC (N-butanol: water: acetic acid=4:1:1). When the reaction was completed, the solvent was evaporated under reduced pressure to afford the crude product, which was recrystallized from methanol/ether to give a white solid.To a suspension of (L)-leucine, (315 g, 2.4 mol) in MeOH (3.2 L) at -15° C. was added SOCl2 (315 mL, 4.32 mol, 1.8 equiv.) dropwise at such a rate that the temp. of the reaction did not exceed 5° C. After the addition was complete, the reaction mixture was allowed to warm to room temp. and was stirred overnight. The resulting mixture was concentrated under reduced pressure and Et2O (3 L) was slowly added to the residue to produce a precipitate. The mixture was cooled with an ice bath, then treated with additional MeOH (3 L) relatively rapidly. After 1 h at 0° C., the crystals were collected and dried to give (L)-leucine methyl ester HCl salt as a white crystalline solid (394 g, 86percent): mp 147-149° C.; 1H-NMR (CD3OD) δ0.78-0.98 (m, 6 h), 1.58-1.72 (m, 3H), 3.76 (g, 3H), 3.92 (t, J=7.3 Hz, 1H)To a suspension of l-leusine 26 (1.12 g, 8.54 mmol) in MeOH (9 mL)at -17 °C was slowly added thionylchloride (2.2 mL, 30.3 mmol) with stirring. Then, the mixture was brought tor.t. and stirred for further 18 h. The solution was concentrated in vacuo to give a white solid. The solid was re-crystalized to yield methylester hydrochloride salt 27 (1.12 g, 6.17 mmol72.2 percent).This compound has previously been described(1)

Molecular Weight:181.66
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:181.0869564
Monoisotopic Mass:181.0869564
Topological Polar Surface Area:52.3
Heavy Atom Count:11
Complexity:112
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes