Acetic Anhydride → Lacosamide

A solution of acetic anhydride (262 mg, 2.56 mmol) and (R)-2-amino-N-benzyl-3-methoxypropanamide 1.6 TFA (1000 mg, 2.56 mmol) in 10 mL of DCM and triethylamine (3.6 mL, 25.6 mmol) was added. The resulting solution was stirred at room temperature for three hours. DCM (200 mL) was added to the reaction mixture. The resulting solution was washed with H2O (200 mL), 0.2 N HCl (100 mL), 5% NaHCO3 (100 mL), and then H2O (100 mL) and dried over Na2SO4. A white solid was obtained after the solvent was removed under reduced pressure. The crude product was purified by crystallization from ethyl acetate/hexane (1:1). The desired product was obtained with a purity of 99% (220 mg, yield: 33.0%). 1H NMR (500 MHz, CDCl3) δ 2.05 (s, 3H). 3.39 (s, 3H), 3.45 (t, 1H), 3.84 (m, 1H), 4.48 (s, 2H), 4.56 (m, 1H), 6.44 (br., 1H). 6.74 (br., 1H), 7.28 (m, 3H), 7.36 (m, 2H). LC-MS (m/z) calculated 250.1. Found 251.1 [M+H]+, 273.1 [M+Na]+.

1. washThe resulting solution was washed with H2O (200 mL), 0.2 N HCl (100 mL), 5% NaHCO3 (100 mL)
2. dry with materialH2O (100 mL) and dried over Na2SO4
3. customA white solid was obtained after the solvent
4. customwas removed under reduced pressure
5. customThe crude product was purified by crystallization from ethyl acetate/hexane (1:1)

ORD record

ord-5953d8f6fa6c4fd48362cbbf9531861d

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09226971B2