Benzylamine → Lacosamide

HRID 2280361ノート

反応式

HRID 2280361 の反応式
[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]

参加物

6

反応物 4

HCID 7504BenzylamineHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 10558933(2R)-2-acetamido-3-methoxypropanoic acid

生成物 1

HCID 219078Lacosamide収率 57%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-10 °C

実験手順

(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%.

後処理

  1. temperatureto warm to room temperature
  2. customthe solvent evaporated
  3. dissolutionthe residue dissolved in dichloromethane
  4. 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)
  5. customThe solvent was evaporated
  6. customthe residue crystallized in ethyl acetate

出典と根拠

ORDレコード
ord-a81f8b0b593848c18aba29c6b1b8e73b
出典データセット
uspto-grants-2015_09
特許番号
US09139513B2

反応ノート

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