Benzylamine → Lacosamide

HRID 2280361Notes

Reaction equation

[C:1]([NH:4][C@H:5]([CH2:9][O:10][CH3:11])[C:6]([OH:8])=O)(=[O:3])[CH3:2].ClC(OCC(C)C)=O.CN1CCOCC1.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>O1CCCC1>[C:1]([NH:4][C@H:5]([CH2:9][O:10][CH3:11])[C:6]([NH:34][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:8])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: -10 °C

Procedure

(R)-2-Acetylamino-3-methoxypropionic acid (8.06 g, 0.05 mol) was dissolved in tetrahydrofuran (80 mL). Isobutyl chloroformate (7.8 mL, 0.06 mol) was added at −10° C. within 10 minutes, followed by 4-methylmorpholine (6.6 mL, 0.06 mol), and the mixture was stirred at −10° C. for 40 minutes. A solution of benzylamine (6.55 mL, 0.06 mol) in tetrahydrofuran (10 mL) was then added at −10° C. The mixture was allowed to warm to room temperature, the solvent evaporated and the residue dissolved in dichloromethane. The solution was successively washed with water (30 mL), 1M HCl (30 mL), 5% sodium hydrogencarbonate solution (30 mL) and again with water (30 mL). The solvent was evaporated and the residue crystallized in ethyl acetate to afford the title compound (7.09 g, 57%). LCMS analysis: 98.0%.

Workup

temperatureto warm to room temperature
customthe solvent evaporated
dissolutionthe residue dissolved in dichloromethane
washThe solution was successively washed with water (30 mL), 1M HCl (30 mL), 5% sodium hydrogencarbonate solution (30 mL) and again with water (30 mL)
customThe solvent was evaporated
customthe residue crystallized in ethyl acetate

Sources & evidence

ORD record: ord-a81f8b0b593848c18aba29c6b1b8e73b
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139513B2

Reaction notes

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